Catalytic domain, repeat 2, of phosphatidylserine synthases from gram-negative bacteria; Catalytic domain, repeat 2, 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 1630127681 238 LSVTPLVGLGKS-SLLNKTIFHLMPCAEQKLTICTPYFNLPAILVRNIIQLLREGKKVEIIVGDKTANDFYIPEDEPFKI 316
Cdd:cd09136     1 LSITPLVGLGKRgNQLNRTIRQLIQSAESELIICTPYFNLPRSLVRDIARLLKRGVKVEIIVGDKTANDFYIPPEEPFKT 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1630127681 317 IGALPYLYEINLRRFLSRLQYYVNTDQLVVRLWKDDDNTYHLKGMWVDDKWMLITGNNLNPRAWRLDLENAILIHDPQLE 396
Cdd:cd09136    81 IGALPYLYEINLRRFAKRLQKYIDNGQLNVRLWKDGNNSFHLKGIWVDDRYHLLTGNNLNPRAWRLDLENGLLIHDPQGQ 160

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1630127681 397 LAPQREKELELIREHTTIVKHYRDLQSIADYPVKV 431
Cdd:cd09136   161 LKAQFEKELEQILAHTTRIKHYSQLESIADYPEKV 195

PLD-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1630127681 256 IFHLMPCAEQKLTICTPYFNLPAILVRNIIQLLREGKKVEIIVGDKTAnDFYIPEDEPFKIIGALpYLYEINLRRFLSRL 335
Cdd:pfam13091   1 LIDLINSAKKSIDIATYYFVPDREIIDALIAAAKRGVDVRIILDSNKD-DAGGPKKASLKELRSL-LRAGVEIREYQSFL 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1630127681 336 qyyvntdqlvvrlwkdddNTYHLKGMWVDDKWMLITGNNLNPRAWRLDLENAILIHDPqlELAPQREKELE 406
Cdd:pfam13091  79 ------------------RSMHAKFYIIDGKTVIVGSANLTRRALRLNLENNVVIKDP--ELAQELEKEFD 129

Catalytic domain, repeat 2, of phosphatidylserine synthases from gram-negative bacteria; Catalytic domain, repeat 2, 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 1630127681 238 LSVTPLVGLGKS-SLLNKTIFHLMPCAEQKLTICTPYFNLPAILVRNIIQLLREGKKVEIIVGDKTANDFYIPEDEPFKI 316
Cdd:cd09136     1 LSITPLVGLGKRgNQLNRTIRQLIQSAESELIICTPYFNLPRSLVRDIARLLKRGVKVEIIVGDKTANDFYIPPEEPFKT 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1630127681 317 IGALPYLYEINLRRFLSRLQYYVNTDQLVVRLWKDDDNTYHLKGMWVDDKWMLITGNNLNPRAWRLDLENAILIHDPQLE 396
Cdd:cd09136    81 IGALPYLYEINLRRFAKRLQKYIDNGQLNVRLWKDGNNSFHLKGIWVDDRYHLLTGNNLNPRAWRLDLENGLLIHDPQGQ 160

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1630127681 397 LAPQREKELELIREHTTIVKHYRDLQSIADYPVKV 431
Cdd:cd09136   161 LKAQFEKELEQILAHTTRIKHYSQLESIADYPEKV 195

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 1630127681  17 LPKISQSVDDVDFFYAPADFRETLLEKIASAKQRICIVALYLEQDDGGKGILNALYEAKRQRPELDVRVLVDWHRAQRGR 96
Cdd:cd09134     1 LPKIPQQPEDIDVLYSPKDFRARLLELISNAKKRIYIVALYLEDDEAGREILDALYEAKANNPGLDIKVLVDWHRAQRGL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1630127681  97 IGAAASNTNADWYCRMAQENPgVDVPVYGVPINTREALGVLHFKGFIIDDSVLYSGASLNDVYLHQHDKYRYDRYHLIRN 176
Cdd:cd09134    81 IGAKKSLGNADWYRKIAQRYG-HDVPIYGVPVKTRELFGVLHLKGFIIDDTVLYSGASLNNVYLHQFDKYRYDRYHLIYN 159

                         170
                  ....*....|....
gi 1630127681 177 RKMSDIMFEWVTQN 190
Cdd:cd09134   160 PELADSMVNFIQDY 173

Catalytic domain, repeat 1, of CDP-alcohol phosphatidyltransferase class-II family members; Catalytic domain, repeat 1, of CDP-alcohol phosphatidyltransferase class-II family members, which mainly include gram-negative bacterial phosphatidylserine synthases (PSS; CDP-diacylglycerol--serine O-phosphatidyltransferase, EC 2.7.8.8), yeast phosphatidylglycerophosphate synthase (PGP synthase; CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase, EC 2.7.8.5), and metazoan PGP synthase 1. All members in this subfamily have two HKD motifs (H-x-K-x(4)-D, where x represents any amino acid residue) that characterize the phospholipase D (PLD) superfamily. They may utilize a common two-step ping-pong catalytic mechanism, involving a substrate-enzyme intermediate, to cleave phosphodiester bonds. The two motifs are suggested to constitute the active site involving phosphatidyl group transfer. Phosphatidylserine synthases from gram-positive bacteria and eukaryotes, and prokaryotic phosphatidylglycerophosphate synthases are not members of this subfamily.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1630127681  27 VDFFYAPADFRETLLEKIASAKQRICIVALYLEQDDGGKGILNALYEAKRQRPELDVRVLVDWHRAQRGRIGAAA-SNTN 105
Cdd:cd09102     2 IRFLGSPAEFKTQIIELIRNAKRRVYVASLYWGKDEAGQEILDEIYSVKQENPNLDVSVLIDWHRAQRNLLGSETkSATN 81

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1630127681 106 ADWYCRMAQ----ENPGVDVPV-YGVPINTREALGVLHFKGFIIDDSVLYSGASLNDVYLHqhdkYRYDRYHLIRN 176
Cdd:cd09102    82 ADWYCEQRQtsqlHLLPDDGN*fFGVPINTNEVFGVLHVKGYVFDDTVLLSGANLSNVYFH----YRYDRYVKITH 153

PLD-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1630127681 256 IFHLMPCAEQKLTICTPYFNLPAILVRNIIQLLREGKKVEIIVGDKTAnDFYIPEDEPFKIIGALpYLYEINLRRFLSRL 335
Cdd:pfam13091   1 LIDLINSAKKSIDIATYYFVPDREIIDALIAAAKRGVDVRIILDSNKD-DAGGPKKASLKELRSL-LRAGVEIREYQSFL 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1630127681 336 qyyvntdqlvvrlwkdddNTYHLKGMWVDDKWMLITGNNLNPRAWRLDLENAILIHDPqlELAPQREKELE 406
Cdd:pfam13091  79 ------------------RSMHAKFYIIDGKTVIVGSANLTRRALRLNLENNVVIKDP--ELAQELEKEFD 129

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 1630127681 258 HLMPCAEQKLTICTPYFNLPA--ILVRNIIQLLREGKKVEIIVGDKTANDFYIPEDEPFKIIGALpylyeINLRRFLSRL 335
Cdd:cd00138     5 ELLKNAKESIFIATPNFSFNSadRLLKALLAAAERGVDVRLIIDKPPNAAGSLSAALLEALLRAG-----VNVRSYVTPP 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1630127681 336 QYyvntdqlvvrlwkddDNTYHLKGMWVDDKWMLITGNNLNPRAWRLDLENAILI 390
Cdd:cd00138    80 HF---------------FERLHAKVVVIDGEVAYVGSANLSTASAAQNREAGVLV 119

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 1630127681  38 ETLLEKIASAKQRICIVALYLEQDDGGKgILNALYEAKRQrpELDVRVLVDWHRAQRGRIGAAasntnadwyCRMAQENP 117
Cdd:cd00138     1 EALLELLKNAKESIFIATPNFSFNSADR-LLKALLAAAER--GVDVRLIIDKPPNAAGSLSAA---------LLEALLRA 68

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1630127681 118 GVDVPVYGvpiNTREALGVLHFKGFIIDDSVLY-SGASLNDVYLHQ 162
Cdd:cd00138    69 GVNVRSYV---TPPHFFERLHAKVVVIDGEVAYvGSANLSTASAAQ 111

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 1630127681 258 HLMPCAEQKLTICTPYFNLPAILVRNIIQLLREGKKVEIIVGDKTANDFyipedepfkIIGALPYLYeinlRRFLSRlqy 337
Cdd:cd09159    18 VAIAAARRRIWIANAYFVPDRRLRRALIEAARRGVDVRLLLPGKSDDPL---------TVAASRALY----GKLLRA--- 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1630127681 338 yvntdqlVVRLWKDDDNTYHLKGMWVDDKWMLITGNNLNPRAWRLDLENAILIHDPqlELAPQREKELE 406
Cdd:cd09159    82 -------GVRIFEYQPSMLHAKTAVIDGDWATVGSSNLDPRSLRLNLEANLVVEDP--AFAAQLEELFE 141

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 1630127681  353 DNTYHLKGMWVDDKWMLITGNNLNPRA 379
Cdd:smart00155   2 DGVLHTKLMIVDDEIAYIGSANLDGRS 28

Putative catalytic domain, repeat 1, of vertebrate phospholipases, PLD3, PLD4 and PLD5, viral envelope proteins K4 and p37, and similar proteins; Putative catalytic domain, repeat 1, of vertebrate phospholipases D, PLD3, PLD4, and PLD5 (EC 3.1.4.4), viral envelope proteins (vaccinia virus proteins K4 and p37), and similar proteins. Most family members contain two copies of the HKD motifs (H-x-K-x(4)-D, where x represents any amino acid residue), and have been classified into the phospholipase D (PLD) superfamily. Proteins in this subfamily are associated with Golgi membranes, altering their lipid content by the conversion of phospholipids into phosphatidic acid, which is thought to be involved in the regulation of lipid movement. ADP ribosylation factor (ARF), a small guanosine triphosphate binding protein, might be required activity. The vaccinia virus p37 protein, encoded by the F13L gene, is also associated with Golgi membranes and is required for the envelopment and spread of the extracellular enveloped virus (EEV). The vaccinia virus protein K4, encoded by the HindIII K4L gene, remains to be characterized. Sequence analysis indicates that the vaccinia virus proteins K4 and p37 might have evolved from one or more captured eukaryotic genes involved in cellular lipid metabolism. Up to date, no catalytic activity of PLD3 has been shown. Furthermore, due to the lack of functional important histidine and lysine residues in the HKD motif, mammalian PLD5 has been characterized as an inactive PLD. The poxvirus p37 proteins may also lack PLD enzymatic activity, since they contain only one partially conserved HKD motif (N-x-K-x(4)-D).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1630127681  38 ETLLEKIASAKQRICIVALY--LEQDDG--------GKGILNALYEAKRQRpeLDVRVLVDwhraqrgriGAAASNTNAD 107
Cdd:cd09106    22 EAWMELISSAKKSIDIASFYwnLRGTDTnpdssaqeGEDIFNALLEAAKRG--VKIRILQD---------KPSKDKPDED 90

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1630127681 108 wyCRMAQENPGVDVpvYGVPINTREALGVLHFKGFIIDDSVLYSG-ASL 155
Cdd:cd09106    91 --DLELAALGGAEV--RSLDFTKLIGGGVLHTKFWIVDGKHFYLGsANL 135

PLD-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1630127681  40 LLEKIASAKQRICIVALYLEQDdggKGILNALYEAKRqRPeLDVRVLVDwhrAQRGRIGAAASNTNADWycrMAQENPGV 119
Cdd:pfam13091   1 LIDLINSAKKSIDIATYYFVPD---REIIDALIAAAK-RG-VDVRIILD---SNKDDAGGPKKASLKEL---RSLLRAGV 69

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1630127681 120 DVPVYGVpintreALGVLHFKGFIIDDSVLYSGaSLN 156
Cdd:pfam13091  70 EIREYQS------FLRSMHAKFYIIDGKTVIVG-SAN 99

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 1630127681  29 FFYAPADFRETLLEKIASAKQRICIVAlYLEQDdggKGILNALYEAkRQRpELDVRVLVDwhraqrgriGAAASNTNADW 108
Cdd:cd09127     2 LFVQPDDGVAPVVDAIASAKRSILLKM-YEFTD---PALEKALAAA-AKR-GVRVRVLLE---------GGPVGGISRAE 66

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1630127681 109 YCRMAQENPGVDVPVYgvpiNTREALGVLHFKGFIIDDS 147
Cdd:cd09127    67 KLLDYLNEAGVEVRWT----NGTARYRYTHAKYIVVDDE 101

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
                  ....*....|....*....|....*....|....*.
gi 1630127681 357 HLKGMWVDDKWMLITGNNLNPRAWRLDLENAILIHD 392
Cdd:cd09105   111 HSKVVIVDDEWATVGSANLNRRSMTWDTELNLAVVD 146