Haloacid Dehalogenase-like Hydrolases; The haloacid dehalogenase (HAD) superfamily includes carbon and phosphorus hydrolases such as 2-haloalkonoate dehalogenase, epoxide hydrolase, phosphoserine phosphatase, phosphomannomutase, phosphoglycolate phosphatase, P-type ATPase, among others. These proteins catalyze nucleophilic substitution reactions at phosphorus or carbon centers, using a conserved Asp carboxylate in covalent catalysis. All members possess a conserve alpha/beta core domain, and many also possess a small cap domain, with varying folds and functions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 579537802    1 MNKISKYIAIASLSVAV-TVSAPQTTNSTAFAKssaevqqtqqasipasqkanlgNQNIMAVAWYQNSAEAKALYLQGYN 79
Cdd:TIGR01533   1 MKKTLKITLLAGLSLSVlTLKGCSSAQMKSEGT----------------------AQNTMSVAWMQRSAEYKALYLQAYN 58

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 579537802   80 SAKTQLDKEIKKNKGKhKLAIALDLDETVLDNSPYQGY 117
Cdd:TIGR01533  59 LAKMRLDNNLKKVKDK-KYAIVLDLDETVLDNSPYQGY 95

5'-nucleotidase, lipoprotein e(P4) family; This model represents a set of bacterial lipoproteins belonging to a larger acid phosphatase family (pfam03767), which in turn belongs to the haloacid dehalogenase (HAD) superfamily of aspartate-dependent hydrolases. Members are found on the outer membrane of Gram-negative bacteria and the cytoplasmic membrane of Gram-positive bacteria. Most members have classic lipoprotein signal sequences. A critical role of this 5'-nucleotidase in Haemophilus influenzae is the degradation of external riboside in order to allow transport into the cell. An earlier suggested role in hemin transport is no longer current. This enzyme may also have other physiologically significant roles. [Transport and binding proteins, Other, Biosynthesis of cofactors, prosthetic groups, and carriers, Pyridine nucleotides]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 579537802    1 MNKISKYIAIASLSVAV-TVSAPQTTNSTAFAKssaevqqtqqasipasqkanlgNQNIMAVAWYQNSAEAKALYLQGYN 79
Cdd:TIGR01533   1 MKKTLKITLLAGLSLSVlTLKGCSSAQMKSEGT----------------------AQNTMSVAWMQRSAEYKALYLQAYN 58

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 579537802   80 SAKTQLDKEIKKNKGKhKLAIALDLDETVLDNSPYQGY 117
Cdd:TIGR01533  59 LAKMRLDNNLKKVKDK-KYAIVLDLDETVLDNSPYQGY 95

molecular class C acid phosphatases, similar to Haemophilus influenzae e (P4) acid phosphatase; belongs to the haloacid dehalogenase-like hydrolase superfamily; Molecular class C acid phosphatases (CAPs) are nonspecific acid phosphatases with generally broad substrate specificity and optimum activity at neutral to acidic pH. Members include Haemophilus influenzae lipoprotein e (P4), Elizabethkingia meningosepticum OlpA, Helicobacter pylori HppA, Enterobacter sp. 4 acid phosphatase PhoI, and Streptococcus pyogenes M1 GAS LppC. Lipoprotein e (P4) exhibits phosphomonoesterase activity with aryl phosphate substrates including nicotinamide mononucleotide (NMN), tyrosine phosphate, phenyl phosphate, p-nitrophenyl phosphate, and 4-methylumbelliferyl phosphate. The role of P4 in NAD+ uptake appears to be the dephosphorylation of NMN to nicotinamide riboside, which is then taken up by the organism. Elizabethkingia meningosepticum OlpA is a broad-spectrum nucleotidase with preference for 5'-nucleotides, it efficiently hydrolyzes nucleotide monophosphates, with a strong preference for 5'-nucleotides and for 3'-AMP; OlpA can also hydrolyze sugar phosphates and beta-glycerol phosphate, although with a lower efficiency. Helicobacter pylori HppA is also a 5' nucleotidase. Members of this family belong to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 579537802  67 SAEAKALYLQGYNSAKTQLDKEIKKNKGKHKLAIALDLDETVLDNSPYQGYD 118
Cdd:cd07534    1 SAEYKALYLQAYNLAKMRLDHALKKEKTDKKPAVVLDLDETVLDNSPYQARQ 52

5'-nucleotidase, lipoprotein e(P4) family; This model represents a set of bacterial lipoproteins belonging to a larger acid phosphatase family (pfam03767), which in turn belongs to the haloacid dehalogenase (HAD) superfamily of aspartate-dependent hydrolases. Members are found on the outer membrane of Gram-negative bacteria and the cytoplasmic membrane of Gram-positive bacteria. Most members have classic lipoprotein signal sequences. A critical role of this 5'-nucleotidase in Haemophilus influenzae is the degradation of external riboside in order to allow transport into the cell. An earlier suggested role in hemin transport is no longer current. This enzyme may also have other physiologically significant roles. [Transport and binding proteins, Other, Biosynthesis of cofactors, prosthetic groups, and carriers, Pyridine nucleotides]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 579537802    1 MNKISKYIAIASLSVAV-TVSAPQTTNSTAFAKssaevqqtqqasipasqkanlgNQNIMAVAWYQNSAEAKALYLQGYN 79
Cdd:TIGR01533   1 MKKTLKITLLAGLSLSVlTLKGCSSAQMKSEGT----------------------AQNTMSVAWMQRSAEYKALYLQAYN 58

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 579537802   80 SAKTQLDKEIKKNKGKhKLAIALDLDETVLDNSPYQGY 117
Cdd:TIGR01533  59 LAKMRLDNNLKKVKDK-KYAIVLDLDETVLDNSPYQGY 95

molecular class C acid phosphatases, similar to Haemophilus influenzae e (P4) acid phosphatase; belongs to the haloacid dehalogenase-like hydrolase superfamily; Molecular class C acid phosphatases (CAPs) are nonspecific acid phosphatases with generally broad substrate specificity and optimum activity at neutral to acidic pH. Members include Haemophilus influenzae lipoprotein e (P4), Elizabethkingia meningosepticum OlpA, Helicobacter pylori HppA, Enterobacter sp. 4 acid phosphatase PhoI, and Streptococcus pyogenes M1 GAS LppC. Lipoprotein e (P4) exhibits phosphomonoesterase activity with aryl phosphate substrates including nicotinamide mononucleotide (NMN), tyrosine phosphate, phenyl phosphate, p-nitrophenyl phosphate, and 4-methylumbelliferyl phosphate. The role of P4 in NAD+ uptake appears to be the dephosphorylation of NMN to nicotinamide riboside, which is then taken up by the organism. Elizabethkingia meningosepticum OlpA is a broad-spectrum nucleotidase with preference for 5'-nucleotides, it efficiently hydrolyzes nucleotide monophosphates, with a strong preference for 5'-nucleotides and for 3'-AMP; OlpA can also hydrolyze sugar phosphates and beta-glycerol phosphate, although with a lower efficiency. Helicobacter pylori HppA is also a 5' nucleotidase. Members of this family belong to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 579537802  67 SAEAKALYLQGYNSAKTQLDKEIKKNKGKHKLAIALDLDETVLDNSPYQGYD 118
Cdd:cd07534    1 SAEYKALYLQAYNLAKMRLDHALKKEKTDKKPAVVLDLDETVLDNSPYQARQ 52