NAD(P) binding domain of Shikimate dehydrogenase; Shikimate dehydrogenase (DH) is an amino acid DH family member. Shikimate pathway links metabolism of carbohydrates to de novo biosynthesis of aromatic amino acids, quinones and folate. It is essential in plants, bacteria, and fungi but absent in mammals, thus making enzymes involved in this pathway ideal targets for broad spectrum antibiotics and herbicides. Shikimate DH catalyzes the reduction of 3-hydroshikimate to shikimate using the cofactor NADH. Amino acid DH-like NAD(P)-binding domains are members of the Rossmann fold superfamily and include glutamate, leucine, and phenylalanine DHs, methylene tetrahydrofolate DH, methylene-tetrahydromethanopterin DH, methylene-tetrahydropholate DH/cyclohydrolase, Shikimate DH-like proteins, malate oxidoreductases, and glutamyl tRNA reductase. Amino acid DHs catalyze the deamination of amino acids to keto acids with NAD(P)+ as a cofactor. The NAD(P)-binding Rossmann fold superfamily includes a wide variety of protein families including NAD(P)- binding domains of alcohol DHs, tyrosine-dependent oxidoreductases, glyceraldehyde-3-phosphate DH, lactate/malate DHs, formate/glycerate DHs, siroheme synthases, 6-phosphogluconate DHs, amino acid DHs, repressor rex, NAD-binding potassium channel domain, CoA-binding, and ornithine cyclodeaminase-like domains. These domains have an alpha-beta-alpha configuration. NAD binding involves numerous hydrogen and van der Waals contacts.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 141906181   6 TDWAGFHDSLKKFylptLKNLDEKNIFILGAGGVSASIIYSLKKLGG-NIFVTNRTKKNAEDLKKLFPN----INIITWG 80
Cdd:cd01065    1 TDGLGFVRALEEA----GIELKGKKVLILGAGGAARAVAYALAELGAaKIVIVNRTLEKAKALAERFGElgiaIAYLDLE 76

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 141906181  81 KKPPKCDVVINTTSIGLNKNDKIDLDFNDYNKDELFYDLIYNPIETNFLKEARLRGNQTTNGKMMFLNQAAYAFYHWTG 159
Cdd:cd01065   77 ELLAEADLIINTTPVGMKPGDELPLPPSLLKPGGVVYDVVYNPLETPLLKEARALGAKTIDGLEMLVYQAAEAFELWTG 155

shikimate dehydrogenase; This model finds proteins from prokaryotes and functionally equivalent domains from larger, multifunctional proteins of fungi and plants. Below the trusted cutoff of 180, but above the noise cutoff of 20, are the putative shikimate dehydrogenases of Thermotoga maritima and Mycobacterium tuberculosis, and uncharacterized paralogs of shikimate dehydrogenase from E. coli and H. influenzae. The related enzyme quinate 5-dehydrogenase scores below the noise cutoff. A neighbor-joining tree, constructed with quinate 5-dehydrogenases as the outgroup, shows the Clamydial homolog as clustering among the shikimate dehydrogenases, although the sequence is unusual in the degree of sequence divergence and the presence of an additional N-terminal domain. [Amino acid biosynthesis, Aromatic amino acid family]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 141906181    2 IGTNTDWAGFHDSLKKfyLPTLKNldEKNIFILGAGGVSASIIYSLKKLGGNIFVTNRTKKNAEDLKKLFP-NINIITWG 80
Cdd:TIGR00507  95 VGYNTDGIGLVSDLEQ--LIPLRP--NQNVLIIGAGGAAKAVALELLKADCNVIIANRTVSKAEELAERFQrYGEIQAFS 170

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 141906181   81 K---KPPKCDVVINTTSIGLNKN-DKIDLDFNDYNKDELFYDLIYNPIETNFLKEARLRGNQTTNGKMMFLNQAAYAFYH 156
Cdd:TIGR00507 171 MdelPLHRVDLIINATSAGMSGNiDEPPVPAEYLKEGKLVYDLVYNPLETPFLAEAKSLGTKTIDGLGMLVYQAALSFEL 250

                  ....*...
gi 141906181  157 WTGQLPEI 164
Cdd:TIGR00507 251 WTGVEPDI 258

NAD(P) binding domain of Shikimate dehydrogenase; Shikimate dehydrogenase (DH) is an amino acid DH family member. Shikimate pathway links metabolism of carbohydrates to de novo biosynthesis of aromatic amino acids, quinones and folate. It is essential in plants, bacteria, and fungi but absent in mammals, thus making enzymes involved in this pathway ideal targets for broad spectrum antibiotics and herbicides. Shikimate DH catalyzes the reduction of 3-hydroshikimate to shikimate using the cofactor NADH. Amino acid DH-like NAD(P)-binding domains are members of the Rossmann fold superfamily and include glutamate, leucine, and phenylalanine DHs, methylene tetrahydrofolate DH, methylene-tetrahydromethanopterin DH, methylene-tetrahydropholate DH/cyclohydrolase, Shikimate DH-like proteins, malate oxidoreductases, and glutamyl tRNA reductase. Amino acid DHs catalyze the deamination of amino acids to keto acids with NAD(P)+ as a cofactor. The NAD(P)-binding Rossmann fold superfamily includes a wide variety of protein families including NAD(P)- binding domains of alcohol DHs, tyrosine-dependent oxidoreductases, glyceraldehyde-3-phosphate DH, lactate/malate DHs, formate/glycerate DHs, siroheme synthases, 6-phosphogluconate DHs, amino acid DHs, repressor rex, NAD-binding potassium channel domain, CoA-binding, and ornithine cyclodeaminase-like domains. These domains have an alpha-beta-alpha configuration. NAD binding involves numerous hydrogen and van der Waals contacts.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 141906181   6 TDWAGFHDSLKKFylptLKNLDEKNIFILGAGGVSASIIYSLKKLGG-NIFVTNRTKKNAEDLKKLFPN----INIITWG 80
Cdd:cd01065    1 TDGLGFVRALEEA----GIELKGKKVLILGAGGAARAVAYALAELGAaKIVIVNRTLEKAKALAERFGElgiaIAYLDLE 76

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 141906181  81 KKPPKCDVVINTTSIGLNKNDKIDLDFNDYNKDELFYDLIYNPIETNFLKEARLRGNQTTNGKMMFLNQAAYAFYHWTG 159
Cdd:cd01065   77 ELLAEADLIINTTPVGMKPGDELPLPPSLLKPGGVVYDVVYNPLETPLLKEARALGAKTIDGLEMLVYQAAEAFELWTG 155

shikimate dehydrogenase; This model finds proteins from prokaryotes and functionally equivalent domains from larger, multifunctional proteins of fungi and plants. Below the trusted cutoff of 180, but above the noise cutoff of 20, are the putative shikimate dehydrogenases of Thermotoga maritima and Mycobacterium tuberculosis, and uncharacterized paralogs of shikimate dehydrogenase from E. coli and H. influenzae. The related enzyme quinate 5-dehydrogenase scores below the noise cutoff. A neighbor-joining tree, constructed with quinate 5-dehydrogenases as the outgroup, shows the Clamydial homolog as clustering among the shikimate dehydrogenases, although the sequence is unusual in the degree of sequence divergence and the presence of an additional N-terminal domain. [Amino acid biosynthesis, Aromatic amino acid family]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 141906181    2 IGTNTDWAGFHDSLKKfyLPTLKNldEKNIFILGAGGVSASIIYSLKKLGGNIFVTNRTKKNAEDLKKLFP-NINIITWG 80
Cdd:TIGR00507  95 VGYNTDGIGLVSDLEQ--LIPLRP--NQNVLIIGAGGAAKAVALELLKADCNVIIANRTVSKAEELAERFQrYGEIQAFS 170

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 141906181   81 K---KPPKCDVVINTTSIGLNKN-DKIDLDFNDYNKDELFYDLIYNPIETNFLKEARLRGNQTTNGKMMFLNQAAYAFYH 156
Cdd:TIGR00507 171 MdelPLHRVDLIINATSAGMSGNiDEPPVPAEYLKEGKLVYDLVYNPLETPFLAEAKSLGTKTIDGLGMLVYQAALSFEL 250

                  ....*...
gi 141906181  157 WTGQLPEI 164
Cdd:TIGR00507 251 WTGVEPDI 258

shikimate dehydrogenase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 141906181   2 IGTNTDWAGFHDSLKKFYLptlkNLDEKNIFILGAGGvSASIIYSLKKLGG----NIFVTN-----RTKKNAEDLKKLFP 72
Cdd:PRK12548 104 TGHITDGLGFVRNLREHGV----DVKGKKLTVIGAGG-AATAIQVQCALDGakeiTIFNIKddfyeRAEQTAEKIKQEVP 178

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 141906181  73 N--INIITWGKKP------PKCDVVINTTSIGLNKNDKIDL--DFNDYNKDELFYDLIYNPIETNFLKEARLRGNQTTNG 142
Cdd:PRK12548 179 EciVNVYDLNDTEklkaeiASSDILVNATLVGMKPNDGETNikDTSVFRKDLVVADTVYNPKKTKLLEDAEAAGCKTVGG 258

                        170
                 ....*....|....*...
gi 141906181 143 KMMFLNQAAYAFYHWTGQ 160
Cdd:PRK12548 259 LGMLLWQGAEAYKLYTGK 276

bifunctional 3-dehydroquinate dehydratase/shikimate dehydrogenase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 141906181  29 KNIFILGAGGVSASIIYSLKKLGGNIFVTNRTKKNAEDLKKLFpNINIITWGK----KPPKCDVVINTTSIGLNKN-DKI 103
Cdd:PLN02520 380 KLFVVIGAGGAGKALAYGAKEKGARVVIANRTYERAKELADAV-GGQALTLADlenfHPEEGMILANTTSVGMQPNvDET 458

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 141906181 104 DLDFNDYNKDELFYDLIYNPIETNFLKEARLRGNQTTNGKMMFLNQAAYAFYHWTGqLP 162
Cdd:PLN02520 459 PISKHALKHYSLVFDAVYTPKITRLLREAEESGAIIVSGTEMFIRQAYEQFERFTG-LP 516

NADP-binding domain of glutamyl-tRNA reductase; Glutamyl-tRNA reductase catalyzes the conversion of glutamyl-tRNA to glutamate-1-semialdehyde, initiating the synthesis of tetrapyrrole. Whereas tRNAs are generally associated with peptide bond formation in protein translation, here the tRNA activates glutamate in the initiation of tetrapyrrole biosynthesis in archaea, plants and many bacteria. In the first step, activated glutamate is reduced to glutamate-1-semi-aldehyde via the NADPH dependent glutamyl-tRNA reductase. Glutamyl-tRNA reductase forms a V-shaped dimer. Each monomer has 3 domains: an N-terminal catalytic domain, a classic nucleotide binding domain, and a C-terminal dimerization domain. Although the representative structure 1GPJ lacks a bound NADPH, a theoretical binding pocket has been described. (PMID 11172694). Amino acid dehydrogenase (DH)-like NAD(P)-binding domains are members of the Rossmann fold superfamily and include glutamate, leucine, and phenylalanine DHs, methylene tetrahydrofolate DH, methylene-tetrahydromethanopterin DH, methylene-tetrahydropholate DH/cyclohydrolase, Shikimate DH-like proteins, malate oxidoreductases, and glutamyl tRNA reductase. Amino acid DHs catalyze the deamination of amino acids to keto acids with NAD(P)+ as a cofactor. The NAD(P)-binding Rossmann fold superfamily includes a wide variety of protein families including NAD(P)- binding domains of alcohol DHs, tyrosine-dependent oxidoreductases, glyceraldehyde-3-phosphate DH, lactate/malate DHs, formate/glycerate DHs, siroheme synthases, 6-phosphogluconate DH, amino acid DHs, repressor rex, NAD-binding potassium channel domain, CoA-binding, and ornithine cyclodeaminase-like domains. These domains have an alpha-beta-alpha configuration. NAD binding involves numerous hydrogen and van der Waals contacts.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 141906181  25 NLDEKNIFILGAGGVSASIIYSLKKLGG-NIFVTNRTKKNAEDLKKLFpNINIITW---GKKPPKCDVVINTTS 94
Cdd:cd05213  175 NLKGKKVLVIGAGEMGELAAKHLAAKGVaEITIANRTYERAEELAKEL-GGNAVPLdelLELLNEADVVISATG 247

quinate/shikimate dehydrogenase; Reviewed

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 141906181   3 GTNTDWAGFHDSLKKFYLptlkNLDEKNIFILGAGGVSASI-----IYSLKKlggnIFVTNRTKKNAEDLKKLFPNIN-- 75
Cdd:PRK12749 103 GYNTDGTGHIRAIKESGF----DIKGKTMVLLGAGGASTAIgaqgaIEGLKE----IKLFNRRDEFFDKALAFAQRVNen 174

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 141906181  76 ---IIT---------WGKKPPKCDVVINTTSIGLN--KNDKIDLDFNDYNKDELFYDLIYNPIETNFLKEARLRGNQTTN 141
Cdd:PRK12749 175 tdcVVTvtdladqqaFAEALASADILTNGTKVGMKplENESLVNDISLLHPGLLVTECVYNPHMTKLLQQAQQAGCKTID 254

                        170
                 ....*....|....*....
gi 141906181 142 GKMMFLNQAAYAFYHWTGQ 160
Cdd:PRK12749 255 GYGMLLWQGAEQFTLWTGK 273

Medium chain reductase/dehydrogenase (MDR)/zinc-dependent alcohol dehydrogenase-like family; The medium chain reductase/dehydrogenases (MDR)/zinc-dependent alcohol dehydrogenase-like family, which contains the zinc-dependent alcohol dehydrogenase (ADH-Zn) and related proteins, is a diverse group of proteins related to the first identified member, class I mammalian ADH. MDRs display a broad range of activities and are distinguished from the smaller short chain dehydrogenases (~ 250 amino acids vs. the ~ 350 amino acids of the MDR). The MDR proteins have 2 domains: a C-terminal NAD(P) binding-Rossmann fold domain of a beta-alpha form and an N-terminal catalytic domain with distant homology to GroES. The MDR group contains a host of activities, including the founding alcohol dehydrogenase (ADH) , quinone reductase, sorbitol dehydrogenase, formaldehyde dehydrogenase, butanediol DH, ketose reductase, cinnamyl reductase, and numerous others. The zinc-dependent alcohol dehydrogenases (ADHs) catalyze the NAD(P)(H)-dependent interconversion of alcohols to aldehydes or ketones. ADH-like proteins typically form dimers (typically higher plants, mammals) or tetramers (yeast, bacteria), and generally have 2 tightly bound zinc atoms per subunit, a catalytic zinc at the active site and a structural zinc in a lobe of the catalytic domain. The active site zinc is coordinated by a histidine, two cysteines, and a water molecule. The second zinc seems to play a structural role, affects subunit interactions, and is typically coordinated by 4 cysteines. Other MDR members have only a catalytic zinc, and some contain no coordinated zinc.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 141906181  29 KNIFILGAGGVSASIIYSLKKLGGNIFVTNRTKKNAEDLKKLF---------PNINIITWGKKPPKCDVVINTT 93
Cdd:cd05188  136 DTVLVLGAGGVGLLAAQLAKAAGARVIVTDRSDEKLELAKELGadhvidykeEDLEEELRLTGGGGADVVIDAV 209

Shikimate 5'-dehydrogenase C-terminal domain; This domain is found in the C-terminal region of Shikimate 5'-dehydrogenase (SDH) present in Methanocaldococcus jannaschii. SDH catalyzes the NADPH-dependent reduction of 3-dehydroshikimate to shikimate in the shikimate pathway. The domain is found just after the C-terminal domain (pfam01488) which is responsible for NADP binding.

                          10        20
                  ....*....|....*....|....*.
gi 141906181  145 MFLNQAAYAFYHWTGQLPEInnEVIR 170
Cdd:pfam18317   4 MLVEQGAEQFELWTGREPPV--EVMR 27

Human Reticulon 4 Interacting Protein 1; Human Reticulon 4 Interacting Protein 1 is a member of the medium chain dehydrogenase/ reductase (MDR) family. Riticulons are endoplasmic reticulum associated proteins involved in membrane trafficking and neuroendocrine secretion. The MDR/zinc-dependent alcohol dehydrogenase-like family, which contains the zinc-dependent alcohol dehydrogenase (ADH-Zn) and related proteins, is a diverse group of proteins related to the first identified member, class I mammalian ADH. MDRs display a broad range of activities and are distinguished from the smaller short chain dehydrogenases (~ 250 amino acids vs. the ~ 350 amino acids of the MDR). The MDR proteins have 2 domains: a C-terminal NAD(P) binding-Rossmann fold domain of a beta-alpha form and an N-terminal catalytic domain with distant homology to GroES.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 141906181  29 KNIFILGA-GGVSASIIYSLKKLGGNIFVTNRTkKNAEDLKKL-------FPNINIITWGKKPPKCDVVINTTSIGLNK 99
Cdd:cd08248  164 KRVLILGGsGGVGTFAIQLLKAWGAHVTTTCST-DAIPLVKSLgaddvidYNNEDFEEELTERGKFDVILDTVGGDTEK 241