Catalytic domain of EDTA-resistant nuclease Nuc from Salmonella typhimurium and similar proteins; Catalytic domain of an EDTA-resistant nuclease Nuc from Salmonella typhimurium and similar proteins. Nuc is an endonuclease cleaving both single- and double-stranded DNA. It is the smallest known member of the phospholipase D (PLD, EC 3.1.4.4) superfamily that includes a diverse group of proteins with various catalytic functions. Most members of this superfamily have two copies of the conserved HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) in a single polypeptide chain and both are required for catalytic activity. However, Nuc only has one copy of the HKD motif per subunit but form a functionally active homodimer (it is most likely also active in solution as a multimeric protein), which has a single active site at the dimer interface containing the HKD motifs from both subunits. Due to the lack of a distinct domain for DNA binding, Nuc cuts DNA non-specifically. It utilizes a two-step mechanism to cleave phosphodiester bonds: Upon substrate binding, the bond is first attacked by a histidine residue from one HKD motif to form a covalent phosphohistidine intermediate, which is then hydrolyzed by water with the aid of a second histidine residue from the other HKD motif in the opposite subunit.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 917539098  15 SIETGYSPEGTALQLVLKTINSAQQEIRLMGYSFTSPEVAGALVRAKQRGLDVKVVLDWKantgrQNKASLAAMNLLVNA 94
Cdd:cd09170    1 TVEVYFSPEGGARELILDVIDSARRSIDVAAYSFTSPPIARALIAAKKRGVDVRVVLDKS-----QAGGKYSALNYLANA 75

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 917539098  95 GIPVRTVSQYKIMHDKVIIADGRNVEVGSFNYTRAADRVNSENVLVVWDVPVVAQHYLRHWQSRWN 160
Cdd:cd09170   76 GIPVRIDDNYAIMHNKVMVIDGKTVITGSFNFTASAEKRNAENLLVIRNPPELAQQYLQEWQRRWA 141

Catalytic domain of EDTA-resistant nuclease Nuc from Salmonella typhimurium and similar proteins; Catalytic domain of an EDTA-resistant nuclease Nuc from Salmonella typhimurium and similar proteins. Nuc is an endonuclease cleaving both single- and double-stranded DNA. It is the smallest known member of the phospholipase D (PLD, EC 3.1.4.4) superfamily that includes a diverse group of proteins with various catalytic functions. Most members of this superfamily have two copies of the conserved HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) in a single polypeptide chain and both are required for catalytic activity. However, Nuc only has one copy of the HKD motif per subunit but form a functionally active homodimer (it is most likely also active in solution as a multimeric protein), which has a single active site at the dimer interface containing the HKD motifs from both subunits. Due to the lack of a distinct domain for DNA binding, Nuc cuts DNA non-specifically. It utilizes a two-step mechanism to cleave phosphodiester bonds: Upon substrate binding, the bond is first attacked by a histidine residue from one HKD motif to form a covalent phosphohistidine intermediate, which is then hydrolyzed by water with the aid of a second histidine residue from the other HKD motif in the opposite subunit.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 917539098  15 SIETGYSPEGTALQLVLKTINSAQQEIRLMGYSFTSPEVAGALVRAKQRGLDVKVVLDWKantgrQNKASLAAMNLLVNA 94
Cdd:cd09170    1 TVEVYFSPEGGARELILDVIDSARRSIDVAAYSFTSPPIARALIAAKKRGVDVRVVLDKS-----QAGGKYSALNYLANA 75

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 917539098  95 GIPVRTVSQYKIMHDKVIIADGRNVEVGSFNYTRAADRVNSENVLVVWDVPVVAQHYLRHWQSRWN 160
Cdd:cd09170   76 GIPVRIDDNYAIMHNKVMVIDGKTVITGSFNFTASAEKRNAENLLVIRNPPELAQQYLQEWQRRWA 141

Phosphatidylserine/phosphatidylglycerophosphate/cardiolipin synthase [Lipid transport and metabolism]; Phosphatidylserine/phosphatidylglycerophosphate/cardiolipin synthase is part of the Pathway/BioSystem: Phospholipid biosynthesis

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 917539098   2 LRFPPPVPAVYAASIETG-YSPEGTALQLVLKTINSAQQEIRLMGYSFT-SPEVAGALVRAKQRGLDVKVVLDWKANTGR 79
Cdd:COG1502  179 LPFPEPAGDVRVQVVPSGpDSPRETIERALLAAIASARRRIYIETPYFVpDRSLLRALIAAARRGVDVRILLPAKSDHPL 258

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 917539098  80 QNKASLAAMNLLVNAGIPVRtvsQYK--IMHDKVIIADGRNVEVGSFNYTRAADRVNSEN 137
Cdd:COG1502  259 VHWASRSYYEELLEAGVRIY---EYEpgFLHAKVMVVDDEWALVGSANLDPRSLRLNFEV 315

Phospholipase D. Active site motifs; Phosphatidylcholine-hydrolyzing phospholipase D (PLD) isoforms are activated by ADP-ribosylation factors (ARFs). PLD produces phosphatidic acid from phosphatidylcholine, which may be essential for the formation of certain types of transport vesicles or may be constitutive vesicular transport to signal transduction pathways. PC-hydrolysing PLD is a homologue of cardiolipin synthase, phosphatidylserine synthase, bacterial PLDs, and viral proteins. Each of these appears to possess a domain duplication which is apparent by the presence of two motifs containing well-conserved histidine, lysine, aspartic acid, and/or asparagine residues which may contribute to the active site. An E. coli endonuclease (nuc) and similar proteins appear to be PLD homologues but possess only one of these motifs. The profile contained here represents only the putative active site regions, since an accurate multiple alignment of the repeat units has not been achieved.

                           10        20
                   ....*....|....*....|....*
gi 917539098   106 IMHDKVIIADGRNVEVGSFNYTRAA 130
Cdd:smart00155   4 VLHTKLMIVDDEIAYIGSANLDGRS 28

Catalytic domain of EDTA-resistant nuclease Nuc from Salmonella typhimurium and similar proteins; Catalytic domain of an EDTA-resistant nuclease Nuc from Salmonella typhimurium and similar proteins. Nuc is an endonuclease cleaving both single- and double-stranded DNA. It is the smallest known member of the phospholipase D (PLD, EC 3.1.4.4) superfamily that includes a diverse group of proteins with various catalytic functions. Most members of this superfamily have two copies of the conserved HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) in a single polypeptide chain and both are required for catalytic activity. However, Nuc only has one copy of the HKD motif per subunit but form a functionally active homodimer (it is most likely also active in solution as a multimeric protein), which has a single active site at the dimer interface containing the HKD motifs from both subunits. Due to the lack of a distinct domain for DNA binding, Nuc cuts DNA non-specifically. It utilizes a two-step mechanism to cleave phosphodiester bonds: Upon substrate binding, the bond is first attacked by a histidine residue from one HKD motif to form a covalent phosphohistidine intermediate, which is then hydrolyzed by water with the aid of a second histidine residue from the other HKD motif in the opposite subunit.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 917539098  15 SIETGYSPEGTALQLVLKTINSAQQEIRLMGYSFTSPEVAGALVRAKQRGLDVKVVLDWKantgrQNKASLAAMNLLVNA 94
Cdd:cd09170    1 TVEVYFSPEGGARELILDVIDSARRSIDVAAYSFTSPPIARALIAAKKRGVDVRVVLDKS-----QAGGKYSALNYLANA 75

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 917539098  95 GIPVRTVSQYKIMHDKVIIADGRNVEVGSFNYTRAADRVNSENVLVVWDVPVVAQHYLRHWQSRWN 160
Cdd:cd09170   76 GIPVRIDDNYAIMHNKVMVIDGKTVITGSFNFTASAEKRNAENLLVIRNPPELAQQYLQEWQRRWA 141

PLD-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 917539098   30 VLKTINSAQQEIRL-MGYSFTSPEVAGALVRAKQRGLDVKVVLD-WKANTGRQNKASLAAMNLLVNAGIPVR-TVSQYKI 106
Cdd:pfam13091   1 LIDLINSAKKSIDIaTYYFVPDREIIDALIAAAKRGVDVRIILDsNKDDAGGPKKASLKELRSLLRAGVEIReYQSFLRS 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 917539098  107 MHDKVIIADGRNVEVGSFNYTRAADRVNSENvLVVWDVPVVAQHYLRHWQSRW 159
Cdd:pfam13091  81 MHAKFYIIDGKTVIVGSANLTRRALRLNLEN-NVVIKDPELAQELEKEFDRLW 132

Putative catalytic domain, repeat 1, of uncharacterized phospholipase D-like proteins; Putative catalytic domain, repeat 1, of uncharacterized phospholipase D (PLD, EC 3.1.4.4)-like proteins. PLD enzymes hydrolyze phospholipid phosphodiester bonds to yield phosphatidic acid and a free polar head group. They can also catalyze transphosphatidylation of phospholipids to acceptor alcohols. Members of this subfamily contain two HKD motifs (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the PLD superfamily. The two motifs may be part of the active site and may be involved in phosphatidyl group transfer.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 917539098  28 QLVLKTINSAQQEIRLMGYSFTSPEVAGALVRAKQRGLDVKVVLDwkaNTGRQNKASL-AAMNLLVNAGIPVRTVS---Q 103
Cdd:cd09127   11 APVVDAIASAKRSILLKMYEFTDPALEKALAAAAKRGVRVRVLLE---GGPVGGISRAeKLLDYLNEAGVEVRWTNgtaR 87

                         90       100
                 ....*....|....*....|....*.
gi 917539098 104 YKIMHDKVIIADGRNVEVGSFNYTRA 129
Cdd:cd09127   88 YRYTHAKYIVVDDERALVLTENFKPS 113

Putative catalytic domain of uncharacterized phospholipase D-like proteins; Putative catalytic domain of uncharacterized phospholipase D (PLD, EC 3.1.4.4)-like proteins. Members of this subfamily contain one copy of HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the PLD superfamily.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 917539098  30 VLKTINSAQQEIRLMGYSFTSPEVAG--------ALVRAKQRGLDVKVVLDWKANTGRQNKASLAAMNLLVNAGIPVRTV 101
Cdd:cd09131    8 LLDLINNAKRSIYIAMYMFKYYENPGngvntlleALIDAHKRGVDVKVVLEDSIDDDEVTEENDNTYRYLKDNGVEVRFD 87

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 917539098 102 SQYKIMHDKVIIADGRNVEVGSFNYTRAADRVNSE 136
Cdd:cd09131   88 SPSVTTHTKLVVIDGRTVYVGSHNWTYSALDYNHE 122

Putative catalytic domain, repeat 1, of uncharacterized hypothetical proteins similar to Nuc, an endonuclease from Salmonella typhimurium; Putative catalytic domain, repeat 1, of uncharacterized hypothetical proteins, which show high sequence homology to the endonuclease from Salmonella typhimurium and vertebrate phospholipase D6. Nuc and PLD6 belong to the phospholipase D (PLD) superfamily. They contain a short conserved sequence motif, the HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue), which characterizes the PLD superfamily and is essential for catalysis. Nuc and PLD6 utilize a two-step mechanism to cleave phosphodiester bonds: Upon substrate binding, the bond is first attacked by a histidine residue from one HKD motif to form a covalent phosphohistidine intermediate, which is then hydrolyzed by water with the aid of a second histidine residue from the other HKD motif in the opposite subunit. However, proteins in this subfamily have two HKD motifs in a single polypeptide chain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 917539098  26 ALQLVLKTINSAQQEIRLMGYSFTSPEVAGALVRAKQRGLDVKVVLDWKANTGRQNKASLAAMNLLVNAGIPVRTVSQyK 105
Cdd:cd09172   10 ALLAFLDEARSAGSSIRLAIYELDDPEIIDALKAAKDRGVRVRIILDDSSVTGDPTEESAAATLSKGPGALVKRRHSS-G 88

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 917539098 106 IMHDKVIIADGRNVEV----GSFNYTRAADRVNSeNVLVVWDVPVVAQHYLRHWQ 156
Cdd:cd09172   89 LMHNKFLVVDRKDGPNrvltGSTNFTTSGLYGQS-NNVLIFRNPAFAAAYLAYWN 142

Catalytic domain of phospholipase D superfamily proteins; Catalytic domain of phospholipase D (PLD) superfamily proteins. The PLD superfamily is composed of a large and diverse group of proteins including plant, mammalian and bacterial PLDs, bacterial cardiolipin (CL) synthases, bacterial phosphatidylserine synthases (PSS), eukaryotic phosphatidylglycerophosphate (PGP) synthase, eukaryotic tyrosyl-DNA phosphodiesterase 1 (Tdp1), and some bacterial endonucleases (Nuc and BfiI), among others. PLD enzymes hydrolyze phospholipid phosphodiester bonds to yield phosphatidic acid and a free polar head group. They can also catalyze the transphosphatidylation of phospholipids to acceptor alcohols. The majority of members in this superfamily contain a short conserved sequence motif (H-x-K-x(4)-D, where x represents any amino acid residue), called the HKD signature motif. There are varying expanded forms of this motif in different family members. Some members contain variant HKD motifs. Most PLD enzymes are monomeric proteins with two HKD motif-containing domains. Two HKD motifs from two domains form a single active site. Some PLD enzymes have only one copy of the HKD motif per subunit but form a functionally active dimer, which has a single active site at the dimer interface containing the two HKD motifs from both subunits. Different PLD enzymes may have evolved through domain fusion of a common catalytic core with separate substrate recognition domains. Despite their various catalytic functions and a very broad range of substrate specificities, the diverse group of PLD enzymes can bind to a phosphodiester moiety. Most of them are active as bi-lobed monomers or dimers, and may possess similar core structures for catalytic activity. They are generally thought to utilize a common two-step ping-pong catalytic mechanism, involving an enzyme-substrate intermediate, to cleave phosphodiester bonds. The two histidine residues from the two HKD motifs play key roles in the catalysis. Upon substrate binding, a histidine from one HKD motif could function as the nucleophile, attacking the phosphodiester bond to create a covalent phosphohistidine intermediate, while the other histidine residue from the second HKD motif could serve as a general acid, stabilizing the leaving group.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 917539098  28 QLVLKTINSAQQEIRLMGYSF---TSPEVAGALVRAKQRGLDVKVVLDWKANTGRQNKASLAAMNLlvNAGIPVRTVSQ- 103
Cdd:cd00138    1 EALLELLKNAKESIFIATPNFsfnSADRLLKALLAAAERGVDVRLIIDKPPNAAGSLSAALLEALL--RAGVNVRSYVTp 78

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 917539098 104 ---YKIMHDKVIIADGRNVEVGSFNYTRAADRVNSEN 137
Cdd:cd00138   79 phfFERLHAKVVVIDGEVAYVGSANLSTASAAQNREA 115

Putative catalytic domain of uncharacterized phospholipase D-like proteins; Putative catalytic domain of uncharacterized phospholipase D (PLD, EC 3.1.4.4)-like proteins. Members of this subfamily contain one copy of HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the PLD superfamily.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 917539098  28 QLVLKTINSAQQEIRLMGYSFTS-PEVAGALVRAKQRGLDVKVVLDW-KANTGRQNKASLAAM-NLLVNAGIPVRTVSQY 104
Cdd:cd09132    2 QVLLELIEGAERSLLIVGYSAYKvSELLQALAAALERGVQVRVVVESsEKAGSVLSLDEDELMwPKLAGATLYVWPEKKR 81

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 917539098 105 K----IMHDKVIIADGRNVEVGSFNYTRAADRVNSE 136
Cdd:cd09132   82 PgkraSLHAKVIVADRRRLLVTSANLTGAGMERNIE 117

Catalytic domain, repeat 2, of Escherichia coli cardiolipin synthase ybhO and similar proteins; Catalytic domain, repeat 2, of Escherichia coli cardiolipin (CL) synthase ybhO and similar proteins. In Escherichia coli, there are two genes, f413 (ybhO) and o493 (ymdC), which are homologous to gene cls that encodes the Escherichia coli CL synthase. The prototype of this subfamily is Escherichia coli CL synthase ybhO specified by the f413 (ybhO) gene. ybhO is a membrane-bound protein that catalyzes the formation of cardiolipin (CL) by transferring phosphatidyl group between two phosphatidylglycerol molecules. It can also catalyze phosphatidyl group transfer to water to form phosphatidate. In contrast to the Escherichia coli CL synthase encoded by the cls gene (EcCLS), ybhO does not hydrolyze CL. Moreover, ybhO lacks an N-terminal segment encoded by Escherichia coli cls, which makes ybhO easy to denature. The monomer of ybhO consists of two catalytic domains. Each catalytic domain contains one copy of the conserved HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the phospholipase D (PLD) superfamily. Two HKD motifs from two domains form a single active site involved in phosphatidyl group transfer. ybhO can be stimulated by phosphate and inhibited by CL, the product of the reaction, and by phosphatidate. Phosphate stimulation may be unique to enzymes with CL synthase activity belonging to the PLD superfamily.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 917539098  25 TALQLVLKTINSAQQEIRL-MGYSFTSPEVAGALVRAKQRGLDVKVVLDWKANTGRQNKASLAAMNLLVNAGIPVRtvsQ 103
Cdd:cd09159   11 SIRRAYLVAIAAARRRIWIaNAYFVPDRRLRRALIEAARRGVDVRLLLPGKSDDPLTVAASRALYGKLLRAGVRIF---E 87

                         90       100
                 ....*....|....*....|....
gi 917539098 104 YK--IMHDKVIIADGRNVEVGSFN 125
Cdd:cd09159   88 YQpsMLHAKTAVIDGDWATVGSSN 111

Putative catalytic domain of uncharacterized hypothetical proteins closely related to Nuc, , an endonuclease from Salmonella typhimurium; Putative catalytic domain of uncharacterized hypothetical proteins, which show high sequence homology to the endonuclease from Salmonella typhimurium and vertebrate phospholipase D6. Nuc and PLD6 belong to the phospholipase D (PLD) superfamily. They contain a short conserved sequence motif, the HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue), which characterizes the PLD superfamily and is essential for catalysis. Nuc and PLD6 utilize a two-step mechanism to cleave phosphodiester bonds: Upon substrate binding, the bond is first attacked by a histidine residue from one HKD motif to form a covalent phosphohistidine intermediate, which is then hydrolyzed by water with the aid of a second histidine residue from the other HKD motif in the opposite subunit. However, proteins in this subfamily have two HKD motifs in a single polypeptide chain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 917539098  34 INSAQQEIRLMGYSFTSPEVAGALVRAKQRGLDVKVVL---DWKANTGR-QNKASLAAMNLlvnagiPVRTVSQYKIMHD 109
Cdd:cd09174   16 IKKAKFSIWIAVAWFTNKDIFNALKNKKKEGVNIQIIInddDINKKDVLiLDEDSFEIYKL------PGNGSRYGNLMHN 89

                         90       100
                 ....*....|....*....|....*...
gi 917539098 110 KVIIADGRNVEVGSFNYTRAADRvNSEN 137
Cdd:cd09174   90 KFCVIDFKTVITGSYNWTKNAEY-NFEN 116

C-terminal domain of Escherichia coli uncharacterized protein yjhR and similar proteins; C-terminal domain of Escherichia coli uncharacterized protein yjhR, encoded by the o338 gene, and similar proteins. Although the biological function of yjhR remains unknown, it shows sequence similarity to the C-terminal portions of superfamily I DNA and RNA helicases, which are ubiquitous enzymes mediating ATP-dependent unwinding of DNA and RNA duplexes, and play essential roles in gene replication and expression. Moreover, The C-termini of yjhR and similar proteins contain one HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the phospholipase D (PLD) superfamily. The PLDc-like domain of yjhR is similar to bacterial endonucleases, Nuc and BfiI, both of which have only one copy of the HKD motif per chain. They function as homodimers, with a single active site at the dimer interface containing the HKD motifs from both subunits. They utilize a two-step mechanism to cleave phosphodiester bonds. Upon substrate binding, the bond is first attacked by a histidine residue from one HKD motif to form a covalent phosphohistidine intermediate, which is then hydrolyzed by water with the aid of a second histidine residue from the other HKD motif in the opposite subunit.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 917539098  60 AKQRGLDVKVVLDWKANTGRQNK---ASLAAMNLLVNAGIPVRTVSQykiMHDKVIIADGRNVEVGSFNYTrAADR 132
Cdd:cd09118   41 AVSRGVDVTIYTDPHLNTGDANDtkaNLEDAAEALAEAGIRIHEVNG---VHSKIVIVDNHLLAVGSFNWL-SAVR 112

Putative catalytic domain, repeat 1, of Escherichia coli uncharacterized protein ymdC and similar proteins; Putative catalytic domain, repeat 1, of Escherichia coli uncharacterized protein ymdC and similar proteins. In Escherichia coli, there are two genes, f413 (ybhO) and o493 (ymdC), which are homologous to gene cls that encodes the Escherichia coli cardiolipin (CL) synthase. The prototype of this subfamily is an uncharacterized protein ymdC specified by the o493 (ymdC) gene. Although the functional characterization of ymdC and similar proteins remains unknown, members of this subfamily show high sequence homology to bacterial CL synthases, which catalyze the reversible phosphatidyl group transfer between two phosphatidylglycerol molecules to form CL and glycerol. Moreover, ymdC and its similar proteins contain two HKD motifs (H-x-K-x(4)-D, where x represents any amino acid residue) that characteriszes the phospholipase D (PLD) superfamily. The two motifs may be part of the active site and may be involved in phosphatidyl group transfer.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 917539098  26 ALQLVLKTINSAQQEIRLMGYSFTSPE----VAGALVRAKQRGLDVKVVLDwKANTGRQNKAsLAAMNLlvNAGIPVR-- 99
Cdd:cd09111    7 ALAARLALIRSAERSIDLQYYIWHDDEsgrlLLGELLEAADRGVRVRLLLD-DLGTSGRDRL-LAALDA--HPNIEVRlf 82

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 917539098 100 --TVSQYKI--------------MHDKVIIAD-------GRNV 119
Cdd:cd09111   83 npFRNRGGRllefltdfsrlnrrMHNKLFIVDgavaivgGRNI 125

Catalytic domain, repeat 2, of vertebrate phospholipases, PLD1 and PLD2, and similar proteins; Catalytic domain, repeat 2, of phospholipase D (PLD, EC 3.1.4.4) found in yeast, plants, and vertebrates, and their bacterial homologs. PLDs are involved in signal transduction, vesicle formation, protein transport, and mitosis by participating in phospholipid metabolism. They hydrolyze the terminal phosphodiester bond of phospholipids resulting in the formation of phosphatidic acid and alcohols. Phosphatidic acid is an essential compound involved in signal transduction. PLDs also catalyze the transphosphatidylation of phospholipids to acceptor alcohols, by which various phospholipids can be synthesized. Both prokaryotic and eukaryotic PLDs have two HKD motifs (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the phospholipase D (PLD) superfamily. PLDs are active as bi-lobed monomers. Each monomer contains two domains, each of which carries one copy of the HKD motif. Two HKD motifs from two domains form a single active site. PLDs utilize a common two-step ping-pong catalytic mechanism involving an enzyme-substrate intermediate to cleave phosphodiester bonds. The two histidine residues from the two HKD motifs play key roles in the catalysis. Upon substrate binding, a histidine residue from one HKD motif could function as the nucleophile, attacking the phosphodiester bond to create a covalent phosphohistidine intermediate, while the other histidine residue from the second HKD motif could serve as a general acid, stabilizing the leaving group.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 917539098  21 SPEGTALQLVLKTINSAQQEIRLMGYSFTSPEVAGALVRA--KQRGLDVKVVL-----DWKANTGRQNKASLAAMNLLVN 93
Cdd:cd09105    4 SGEFEIADAYLKAIRNARRYIYIEDQYLWSPELLDALAEAlkANPGLRVVLVLpalpdAVAFGADDGLDALALLALLLLA 83

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 917539098  94 AGIPVR-----------TVSQYKIM--HDKVIIADGRNVEVGSFN 125
Cdd:cd09105   84 DAAPDRvavfslathrrGLLGGPPIyvHSKVVIVDDEWATVGSAN 128

Catalytic domain, repeat 1, of Escherichia coli cardiolipin synthase and similar proteins; Catalytic domain, repeat 1, of Escherichia coli cardiolipin (CL) synthase and similar proteins. Escherichia coli CL synthase (EcCLS), specified by the cls gene, is the prototype of this family. EcCLS is a multi-pass membrane protein that catalyzes reversible phosphatidyl group transfer between two phosphatidylglycerol molecules to form cardiolipin (CL) and glycerol. The monomer of EcCLS consists of two catalytic domains. Each catalytic domain contains one copy of the conserved HKD motif (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the phospholipase D (PLD) superfamily. Two HKD motifs from two domains form a single active site involved in phosphatidyl group transfer. EcCLS can be stimulated by phosphate and inhibited by CL, the product of the reaction, and by phosphatidate. Phosphate stimulation may be unique to enzymes with CL synthase activity belonging to the PLD superfamily. Like other PLD enzymes, EcCLS utilizes a common two-step ping-pong catalytic mechanism involving an enzyme-substrate intermediate to cleave phosphodiester bonds. The two histidine residues from the two HKD motifs play key roles in the catalysis. Upon substrate binding, a histidine residue from one HKD motif could function as the nucleophile, attacking the phosphodiester bond to create a covalent phosphohistidine intermediate, while the other histidine residue from the second HKD motif could serve as a general acid, stabilizing the leaving group.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 917539098  25 TALQLVLKTINSAQQEIRLMGYSF----TSPEVAGALVRAKQRGLDVKVVLDwKANTGRQNKASLAAMnlLVNAGIPVRT 100
Cdd:cd09152   12 AVIDRLIADIDAAKHHVHLLFYIWaddgTGDRVAEALERAAKRGVTCRLLLD-AVGSRAFFRSSLWKR--LREAGVEVVE 88

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 917539098 101 VSQYKIM-----------HDKVIIADGRNVEVGSFNYTRAADRVNS 135
Cdd:cd09152   89 ALPLRLFrrrlarfdlrnHRKIAVIDGRIAYTGSQNIIDPEFFKKA 134

Putative catalytic domain, repeat 1, of uncharacterized proteins similar to bacterial cardiolipin synthase; Putative catalytic domain, repeat 1, of uncharacterized proteins similar to bacterial cardiolipin (CL) synthases, which catalyze the reversible phosphatidyl group transfer between two phosphatidylglycerol molecules to form CL and glycerol. Members of this subfamily contain two HKD motifs (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the phospholipase D (PLD) superfamily. The two motifs may be part of the active site and may be involved in phosphatidyl group transfer.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 917539098  22 PEGT-ALQLVLKTINSAQQEIRLMGYSF----TSPEVAGALVRAKQRGLDVKVVLD----WKANTGrqnkaslaAMNLLV 92
Cdd:cd09156    1 ADGVeAYQALIQLIESAKHSIDVCTFILgddaTGRRVIDALARKAREGVEVRLLLDalgsFFLSRR--------ALKKLR 72

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 917539098  93 NAG-----------IPVRTVSQYKiMHDKVIIADGRNVEVGSFN 125
Cdd:cd09156   73 AAGgkvaffmpvfrLPFRGRTNLR-NHRKIAIADGSTAISGGMN 115

Catalytic domain, repeat 1, of phosphatidylserine synthases from gram-negative bacteria; Catalytic domain, repeat 1, of phosphatidylserine synthases (PSSs) from gram-negative bacteria. There are two subclasses of PSS enzymes in bacteria: subclass I of gram-negative bacteria and subclass II of gram-positive bacteria. It is common that PSSs in gram-positive bacteria and yeast are tight membrane-associated enzymes. By contrast, the gram-negative bacterial PSSs, such as Escherichia coli PSS, are commonly bound to the ribosomes. They are peripheral membrane proteins that can interact with the surface of the inner membrane by binding to the lipid substrate (CDP-diacylglycerol) and the lipid product (phosphatidylserine). The prototypical member of this subfamily is Escherichia coli PSS (also called CDP-diacylglycerol-L-serine O-phosphatidyltransferase, EC 2.7.8.8), which catalyzes the exchange reactions between CMP and CDP-diacylglycerol, and between serine and phosphatidylserine. The phosphatidylserine is then decarboxylated by phosphatidylserine decarboxylase to yield phosphatidylethanolamine, the major phospholipid in Escherichia coli. It also catalyzes the hydrolysis of CDP-diacylglycerol to form phosphatidic acid with the release of CMP. PSS may utilize a ping-pong mechanism involving a phosphatidyl-enzyme intermediate, which is distinct from those of gram-positive bacterial phosphatidylserine synthases. Moreover, all members in this subfamily have two HKD motifs (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the phospholipase D (PLD) superfamily. The two motifs constitute an active site for the formation of a covalent substrate-enzyme intermediate.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 917539098  10 AVYAASIETGYSPEGTALQLvLKTINSAQQEIRLMGYSFTSPEvAG-----ALVRAKQR--GLDVKVVLDW-KANTGR-Q 80
Cdd:cd09134    5 PQQPEDIDVLYSPKDFRARL-LELISNAKKRIYIVALYLEDDE-AGreildALYEAKANnpGLDIKVLVDWhRAQRGLiG 82

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 917539098  81 NKASL--AAMNLLVNA---------GIPVRTVSQYKIMHDKVIIAD 115
Cdd:cd09134   83 AKKSLgnADWYRKIAQryghdvpiyGVPVKTRELFGVLHLKGFIID 128

Putative catalytic domain, repeat 2, of uncharacterized proteins similar to bacterial cardiolipin synthase; Putative catalytic domain, repeat 2, of uncharacterized proteins similar to bacterial cardiolipin (CL) synthases, which catalyze the reversible phosphatidyl group transfer between two phosphatidylglycerol molecules to form CL and glycerol. Members of this subfamily contain two HKD motifs (H-x-K-x(4)-D, where x represents any amino acid residue) that characterizes the phospholipase D (PLD) superfamily. The two motifs may be part of the active site and may be involved in phosphatidyl group transfer.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 917539098  29 LVLKTINSAQQEIRLMG-YSFTSPEVAGALVRAKQRGLDVKVVLDWKANTGRQNKASLAAMNLLVNAGIPVRtvsqYKIM 107
Cdd:cd09163   15 TLLGAISAARHSIRIMTpYFLPDRTLITALQAAALRGVEVDIVLPERNNLPLVDWAMRANLWELLEHGVRIY----LQPP 90

                         90       100
                 ....*....|....*....|.
gi 917539098 108 ---HDKVIIADGRNVEVGSFN 125
Cdd:cd09163   91 pfdHSKLMVVDGAWALIGSAN 111

Phospholipase D. Active site motifs; Phosphatidylcholine-hydrolyzing phospholipase D (PLD) isoforms are activated by ADP-ribosylation factors (ARFs). PLD produces phosphatidic acid from phosphatidylcholine, which may be essential for the formation of certain types of transport vesicles or may be constitutive vesicular transport to signal transduction pathways. PC-hydrolysing PLD is a homologue of cardiolipin synthase, phosphatidylserine synthase, bacterial PLDs, and viral proteins. Each of these appears to possess a domain duplication which is apparent by the presence of two motifs containing well-conserved histidine, lysine, aspartic acid, and/or asparagine residues which may contribute to the active site. An E. coli endonuclease (nuc) and similar proteins appear to be PLD homologues but possess only one of these motifs. The profile contained here represents only the putative active site regions, since an accurate multiple alignment of the repeat units has not been achieved.

                           10        20
                   ....*....|....*....|....*
gi 917539098   106 IMHDKVIIADGRNVEVGSFNYTRAA 130
Cdd:smart00155   4 VLHTKLMIVDDEIAYIGSANLDGRS 28