1EE9


Conserved Protein Domain Family
NAD_bind_m-THF_DH

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cd01079: NAD_bind_m-THF_DH 
Click on image for an interactive view with Cn3D
NAD binding domain of methylene-tetrahydrofolate dehydrogenase
The NAD-binding domain of methylene-tetrahydrofolate dehydrogenase (m-THF DH). 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. M-THF DH is a component of an unusual monofunctional enzyme; in eukaryotes, m-THF DH is typically found as part of a multifunctional protein. NADP-dependent m-THF DHs 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, monofunctional DH, as well as bifunctional DH/cyclodrolase are found. In addition, yeast (S. cerevisiae) also express an monofunctional DH. This family contains only the monofunctional DHs from S. cerevisiae and certain bacteria. 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.
Statistics
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PSSM-Id: 133447
View PSSM: cd01079
Aligned: 6 rows
Threshold Bit Score: 295.489
Threshold Setting Gi: 116501537
Created: 30-Apr-2009
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
NAD bindingputative
Conserved site includes 11 residues -Click on image for an interactive view with Cn3D
Feature 1:NAD binding site [chemical binding site]
Evidence:
  • 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

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                                                     
1EE9_A    116 KEKDVEGLNHVYYQNLYHNVRYLDke-----------------------nrLKSILPCTPLAIVKILEFLkiynnllpeG 172 baker's yeast
NP_595877 118 PDKDVEGLCHKYVMNMYHNIRHLDpe-----------------------ktKKSILPCTPLAIVKILEYLgvynkiinyG 174 Schizosaccharomyce...
NP_661614 106 PHKDVEGLSPHWIKKLYANERFDDte-----------------------rrFKSILPCTPLAIIKLLEVTeay---apfG 159 Chlorobium tepidum...
AAO50895  117 PTKDIEGLSTQNRFNLYHNIRFMDget----------------------atKKCVIPCTPLAMVKIIDNLgiydkslamG 174 Dictyostelium disc...
CAE76333  121 LSKDVEGLCHTHLFNMYHNVRFLDppt----------------------nlKKSILPCTPLAIVKTLEYLqiynpilayG 178 Neurospora crassa
EAU84432  124 PLKDVEGLHFKFHYNLYHNIRFLKpesllntvsapcettstidgevppegmVKSIIPCTPLAIVKCLEFVgvynrilpyG 203 Coprinopsis cinere...
Feature 1                ###                     ##                                           
1EE9_A    173 NRLYGKKCIVINRSEIVGRPLAALLANDGATVYSVDVNNIQKFTrgesl--------klnkHHVEDlgeysedllkkcsl 244 baker's yeast
NP_595877 175 NRLYGKTITIVNRSEIVGRPLAALLANDGAKVYSVDIHNVQCFTrgagi--------rskkHDVADtnfkle----dvap 242 Schizosaccharomyce...
NP_661614 160 LPFGGQQITIFNRSEVVGRPLAYMLSNDGARVYSFDINGGFVVDvnss---------dhesRPVTReea---------ls 221 Chlorobium tepidum...
AAO50895  175 EHLKGKTVTIVNRSEIVGRPLAAMLANDGAIVYSIDINGIIIFQsgkrhg-----tikmseTNVTReea---------is 240 Dictyostelium disc...
CAE76333  179 NRLFGKTITVINRSEVNGRPLAALLANDGATVYSVDITGVQVFTrgegi--------rqlrHQVHDkegwel---kdvlp 247 Neurospora crassa
EAU84432  204 DRAYGKTVTIINRSEVVGRPLAALLSNDGARVLSVDIDSIQEYTkrprvtadtegaqryhpRHIVQptnmtl---qecla 280 Coprinopsis cinere...
Feature 1            ###                    # #                   #                     
1EE9_A    245 dSDVVITGVPSENY-KFPTEYIKEGAVCINFACT-KNFSDDVKEKAsLYVPMTGKVTIAMLLRNMLRLVRNVEL 316 baker's yeast
NP_595877 243 iSDVIICGVPSANY-KFPSNLVRDGAVCICFSSEkNFDAASLKEHAgIYVPSIGKVTIAMLLRNLIRLTSYQLN 315 Schizosaccharomyces pomb...
NP_661614 222 qSDIVITGVPSPHFeKVRAEELKPGAICLNFSYI-QNFEPEAKEAAsLYIPRVGPMTVAMCMRNALQLYHNYHH 294 Chlorobium tepidum TLS
AAO50895  241 kSDILILGVPSPNY-KVNSDLIQDGTIVINFAGC-LNVDESIQEKS-ILVPTIGKVTIAMLERNLLRLFNNQIS 311 Dictyostelium discoideum
CAE76333  248 lSDVVIGGVPTEKF-KVPTELLRDGAVCINFSSFkNFDGPAVKEKAsIYVPSIGKVTIAVLLRNLVRLIANRPR 320 Neurospora crassa
EAU84432  281 vSDVVVSAVPSATY-KVKTEWLKPGCICLNVAAD-KNFEANVREKAsIYVPAVGKVTILMLLRNLLRLQQYQRV 352 Coprinopsis cinerea okay...

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