1DIA,1B0A,2C2Y


Conserved Protein Domain Family
NAD_bind_m-THF_DH_Cyclohyd

?
cd01080: NAD_bind_m-THF_DH_Cyclohyd 
Click on image for an interactive view with Cn3D
NADP binding domain of methylene-tetrahydrofolate dehydrogenase/cyclohydrolase
NADP binding domain of the Methylene-Tetrahydrofolate Dehydrogenase/cyclohydrolase (m-THF DH/cyclohydrolase) bifunctional enzyme. Tetrahydrofolate 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, monofucntional DH, as well as bifunctional m-THF m-THF DHm-THF DHDH/cyclodrolase are found. In addition, yeast (S. cerevisiae) also express an monofunctional DH. This family contains the bifunctional DH/cyclohydrolase. 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.
Statistics
?
PSSM-Id: 133448
View PSSM: cd01080
Aligned: 53 rows
Threshold Bit Score: 168.888
Threshold Setting Gi: 15805893
Created: 30-Apr-2009
Updated: 2-Oct-2020
Structure
?
Program:
Drawing:
Aligned Rows:
 
NADP bindingsubstratehomodimer
Conserved site includes 12 residues -Click on image for an interactive view with Cn3D
Feature 1:NADP binding site [chemical binding site]
Evidence:
  • Structure:1DIA_A: human bifunctional methylenetetrahydrofolate dehydrogenase cyclohydrolase bound to NADP, contacts determined at 3.5A
    View structure with Cn3D
  • Comment:NRSEIVG interacts with adenine moiety, ASP208 with ribose
  • Comment:Lacks the canonical GXXGXXG Rossmann fold nucleotide binding motif
  • Citation:PMID 9519408

Sequence Alignment
?
Format: Row Display: Color Bits: Type Selection:
Feature 1                                       #                                      ##        
1DIA_A       120 PEKDVDGLTSINAGRLargdl---ndcfIPCTPKGCLELIKETg--------------vPIAGRHAVVVGRSKIVGAPMH 182 human
P47259       106 PLKDVDGLTTNHLAEI------------KPCIVEAIITLKELFn--------------lEFNNQKIVVVGLGITGGKPIY 159 Mycoplasma geni...
AAP57064     137 IRLDVDAFLYHRFDQDqke-------kvIPCVLNAVLELFKEYq--------------lSFLDKKILLIGNGITSNQPIV 195 Mycoplasma gall...
AAT27646     108 ITKDIDGLSEKNSKNLysgk-----sciQPATARGIIDLIKEYn--------------fTIKDKKVYVIGESNLVGKPIK 168 Mycoplasma mobi...
XP_850609      5 VLSLVTCVGTLAHAAGpwlcpppnshtaSMCLWAASLKPTQSVsvtiqehrpaaqsrmgLPAGFPALLPAPSGTSGPGHA 84  dog
YP_645249    115 PLKDIEAVHPVNAGLLalgr-----pryVPSTPAACFYLLDRYlersg------rppeeFYPRSTVVVVGRSNNVGKPAV 183 Rubrobacter xyl...
YP_753270    112 PDKDVDGFSLVNRGRMsgdr-----pgfISCAALACLEVIERFf--------------pSLAGKKAVLVGDSFDLIIPLA 172 Syntrophomonas ...
XP_001017646 131 SEKDADGLKLNSNNLDpka-------niLPCTPAACLKILEEHq--------------iCLKDKHVVLIGRGRLVGQPLE 189 Tetrahymena the...
XP_001023250 138 PSKDVDGLQRCFLTQQliwdd--hnnraLPCTPQSCLHILDTHk--------------iDVKGKQVVMLGKGLLVGSPLG 201 Tetrahymena the...
CAK82784      85 PSKDVDCLHMANFQNLlqnge---dndiIPCTPAAVLHILDTQe--------------iDVRNQNVTVIGRSQLVGFPLS 147 Paramecium tetr...
Feature 1                       ##                     # #  #              # #                   
1DIA_A       183 DLLLw--NNATVTTCHSKTAhlde---evnKGDILVVATGQPEMVKGEWIKPGAIVIDCGINyvpddkkpngrKVVGDVA 257 human
P47259       160 EFLKt--SGYKVQACDKDTPntfe---likSADIVFTAIGKSHFFQAKNFKKGVILFDIGVSrnk------qnKLCGDIN 228 Mycoplasma geni...
AAP57064     196 NYLNe--HQIKFDLITKENSqlle--ektkVADLVISAVGKAKFLANYQFKRGVIFIDIGIDkyfdp-eqskyLICGDFD 270 Mycoplasma gall...
AAT27646     169 ELFKq--AGAIVKSFNINTGikg-----seEADILIVAAGHPNLVKPENVKNNSIVIDVGINsige---ndkmIVTGDVD 238 Mycoplasma mobi...
XP_850609     85 PKLLaqhLLQKDPLSHQYTPkeqlk-kctvLAEIVISAVGILNLITADIIKEGAALINVGINrvqdp-ilskaKLVGDVD 162 dog
YP_645249    184 SLGFa--RGAAVISCDANAYragrlrehtlKADALIVAAGVAGLIDESYVREGVIAVDVGINpvadpggsgrtLLVGDLD 261 Rubrobacter xyl...
YP_753270    173 TIMIk--RACQLSVLPSYEPgl------asGADILVVEKGRAGIVQAEGLAPGVLIIDAGFYwg-------agGVCGNVD 237 Syntrophomonas ...
XP_001017646 190 QLLSk-lSPAQITTCVKETGdikq---hilKADVIIAAAGERQLIKGKWIKKGAIVLDVGVNkgipg--idptKVVGDVE 263 Tetrahymena the...
XP_001023250 202 AILLg--RGAIVSMCDKKSDlsi----alkDADILVSATGVRKLVKGEQLKKGVIVIDVGCSrplph--edqsSIVGDVE 273 Tetrahymena the...
CAK82784     148 VLLLr--RNAKVTICHSETTvqe----hvqKADIVISCAGHKELVKGEWIKNGAKVIDVGITrip-----gtnKIVGDIE 216 Paramecium tetr...
Feature 1                            #  #             
1DIA_A       258 YDEAKer--asFITPVPGGVGPMTVAMLMQSTVESAK 292 human
P47259       229 PEGIEkk--arWWTKTPGGVGPFTVLAIIKNLWILHE 263 Mycoplasma genitalium
AAP57064     271 YDKLKei--asYGTPTPGGIGPLTIYSLVKNLINLSE 305 Mycoplasma gallisepticum R
AAT27646     239 FSNVKtk--vkAISPVPGGVGPMTVISLFKNLIEIFE 273 Mycoplasma mobile 163K
XP_850609    163 FEGIRkn---aNYITPVWGVGPMTVAMLMKNTIIAAK 196 dog
YP_645249    262 FGSVArk--aeALTPVPGGVGPITDVWLLKNTVAAGR 296 Rubrobacter xylanophilus DSM 9941
YP_753270    238 RAALErqgfeaRLLPVPGGMGPILIAKLMENLAQAAR 274 Syntrophomonas wolfei subsp. wolfei str. Goettingen
XP_001017646 264 FEEAKkr--asLITPVPGGIGPMTVSMLMYNTVQIWK 298 Tetrahymena thermophila SB210
XP_001023250 274 FESAS------LLTPVPGGVGPVTVSMLIQNVVKQWE 304 Tetrahymena thermophila SB210
CAK82784     217 FQKALsk--vsFITPVPGGVGPLTVSMLFKNLYRVWC 251 Paramecium tetraurelia

| Disclaimer | Privacy statement | Accessibility |
NCBI Home NCBI Search NCBI SiteMap