Conserved Protein Domain Family

cd05212: NAD_bind_m-THF_DH_Cyclohyd_like 
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NAD(P) binding domain of methylene-tetrahydrofolate dehydrogenase and methylene-tetrahydrofolate dehydrogenase/cyclohydrolase
NAD(P) binding domains of methylene-tetrahydrofolate dehydrogenase (m-THF DH) and m-THF DH/cyclohydrolase bifunctional enzymes (m-THF DH/cyclohydrolase). M-THF is a versatile carrier of activated one-carbon units. The major one-carbon folate donors are N-5 methyltetrahydrofolate, N5,N10-m-THF, and N10-formayltetrahydrofolate. The oxidation of metabolic intermediate m-THF to m-THF requires the enzyme m-THF DH. In addition, most DHs also have an associated cyclohydrolase activity which catalyzes its hydrolysis to N10-formyltetrahydrofolate. m-THF DH is typically found as part of a multifunctional protein in eukaryotes. NADP-dependent m-THF DH in mammals, birds and yeast are components of a trifunctional enzyme with DH, cyclohydrolase, and synthetase activities. Certain eukaryotic cells also contain homodimeric bifunctional DH/cyclodrolase form. In bacteria, mono-functional DH, as well as bifunctional DH/cyclodrolase are found. In addition, yeast (S. cerevisiae) also express a monofunctional DH. M-THF DH, like other amino acid DH-like NAD(P)-binding domains, is a member of the Rossmann fold superfamily which includes glutamate, leucine, and phenylalanine DHs, m-THF DH, methylene-tetrahydromethanopterin DH, m-THF 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.
PSSM-Id: 133451
Aligned: 5 rows
Threshold Bit Score: 183.862
Created: 15-Nov-2004
Updated: 2-Oct-2020
Aligned Rows:
NAD(P) binding
Conserved site includes 6 residues -Click on image for an interactive view with Cn3D
Feature 1:NAD(P) binding site [chemical binding site]
  • Structure:1DIA_A: human bifunctional methylenetetrahydrofolate dehydrogenase cyclohydrolase bound to NADP, contacts determined at 3.5A
    View structure with Cn3D
  • Citation:PMID 9519408
  • Structure:1EE9_A: yeast methylenetetrahydrofolate dehydrogenase cyclohydrolase bound to NAD, contacts determined at 3.5A
    View structure with Cn3D
  • Comment:Lacks the canonical GXXGXXG Rossmann fold nucleotide binding motif
  • Comment:NRSEIVG interacts with adenine moiety, ASP208 with ribose

Sequence Alignment
Format: Row Display: Color Bits: Type Selection:
Feature 1                                           ##                     ##                  
1EE9_A     148 LPCTPLAIVKILEFLkiynnllpegnrlYGKKCIVINRSEIVGRPLAALLAnDGATVYSVDVNNiqkftrgeslklnkhh 227  baker's yeast
AAQ82696   193 GDAHECFVSPVAKAViellek--sgvnlDGKKILVVGAHGSLEAALQCLFQrKGSMTMSIQWKTrqlqs----------- 259  human
CAG03593   118 GDLSAGFVPPVTSAVlewlsk--hhvtlEGKTVLILGGHGTFEVTLRCLIErQGIEVVVSDWTSknlks----------- 184  Tetraodon nigrov...
XP_419672  226 GEDSDYFVSPTAGAVmell------edlDGKTVLLVGINGALGSSLQCLLQrRGAITASCLWKSpglqs----------- 288  chicken
Feature 1                               #                    #                                 
1DIA_A     205 --------------evnkGDILVVATGqp-emVKGEWIKPGAIVIDCGinyvpddkkpngrkvvgdvaYDEAKerasFIT 269  human
1EE9_A     228 vedlgeysedllkkcsldSDVVITGVPsenykFPTEYIKEGAVCINFActk---------------nfSDDVKekasLYV 292  baker's yeast
AAQ82696   260 --------------klheADIVVLGSPkp-eeIPLTWIQPGTTVLNCShdf---------------lsGKVGCgsprIHF 309  human
CAG03593   185 --------------qvmrADAVVVLEAgk-knLPPTWFKPGALVFSCDpts---------------ktDESVAes-sSNS 233  Tetraodon nigrov...
XP_419672  289 --------------klhhADVVVAGSPkp-dsVPKSWLKPGTTIINCSpdl---------------lsGRQSLncgsVKA 338  chicken
Feature 1                                  
1DIA_A     270 PVpg-----gvGPMTVAMLMQSTVESAK 292  human
1EE9_A     293 PMt--------GKVTIAMLLRNMLRLVR 312  baker's yeast
AAQ82696   310 GGliee--ddvILLAAALRIQNMVSSGR 335  human
CAG03593   234 GL---------GYLTAAYRMKNVAQSCG 252  Tetraodon nigroviridis
XP_419672  339 VWgnnttenavCSLAVAMRMQNMVKNTE 366  chicken

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