2JL1,1K6I,2EXX


Conserved Protein Domain Family
NmrA_TMR_like_SDR_a

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cd08947: NmrA_TMR_like_SDR_a 
Click on image for an interactive view with Cn3D
NmrA (a transcriptional regulator), HSCARG (an NADPH sensor), and triphenylmethane reductase (TMR) like proteins, atypical (a) SDRs
Atypical SDRs belonging to this subgroup include NmrA, HSCARG, and TMR, these proteins bind NAD(P) but they lack the usual catalytic residues of the SDRs. Atypical SDRs are distinct from classical SDRs. NmrA is a negative transcriptional regulator of various fungi, involved in the post-translational modulation of the GATA-type transcription factor AreA. NmrA lacks the canonical GXXGXXG NAD-binding motif and has altered residues at the catalytic triad, including a Met instead of the critical Tyr residue. NmrA may bind nucleotides but appears to lack any dehydrogenase activity. HSCARG has been identified as a putative NADP-sensing molecule, and redistributes and restructures in response to NADPH/NADP ratios. Like NmrA, it lacks most of the active site residues of the SDR family, but has an NAD(P)-binding motif similar to the extended SDR family, GXXGXXG. TMR, an NADP-binding protein, lacks the active site residues of the SDRs but has a glycine rich NAD(P)-binding motif that matches the extended SDRs. Atypical SDRs include biliverdin IX beta reductase (BVR-B,aka flavin reductase), NMRa (a negative transcriptional regulator of various fungi), progesterone 5-beta-reductase like proteins, phenylcoumaran benzylic ether and pinoresinol-lariciresinol reductases, phenylpropene synthases, eugenol synthase, triphenylmethane reductase, isoflavone reductases, and others. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold, an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Sequence identity between different SDR enzymes is typically in the 15-30% range; they catalyze a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing. Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase numbering). In addition to the Tyr and Lys, there is often an upstream Ser and/or an Asn, contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. In addition to the Rossmann fold core region typical of all SDRs, extended SDRs have a less conserved C-terminal extension of approximately 100 amino acids, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif.
Statistics
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PSSM-Id: 187651
Aligned: 4 rows
Threshold Bit Score: 289.06
Created: 24-Mar-2010
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
NADP binding
Conserved site includes 15 residues -Click on image for an interactive view with Cn3D
Feature 1:NADP binding site [chemical binding site]
Evidence:
  • Structure:2JL1_A: Citrobacter sp. triphenylmethane reductase binds NADP, contacts at 4A
  • Structure:2EXX_A: human HSCARG binds NADP, contacts at 4A
  • Comment:GxxGxxG NADP-binding motif; this is absent in NmrA

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1         # ####                     #                     ###                   ###  
2JL1_A      3 IAVTGATGQLGGLVIQHLLkkvpasqIIAIVRNvekas---tladqGVEVRHGDYNqp-eSLQKAFaGVSKLLFISGPhy 78  Citrobacter sp. MY-5
1K6I_A      8 IAVVNATGRQAASLIRVAAavg--hhVRAQVHSlkgliaeelqaipNVTLFQGPLLnnvpLMDTLFeGAHLAFINTTSqa 85  Emericella nidulans
YP_625387   2 YAITGITGKVGGALARELLasg--rpVRAVVRDatraa---awaarGCEIATAFMEap-aLLADAFaGATGVFILLPPvf 75  Burkholderia cenoc...
2EXX_A     14 VVVFGGTGAQGGSVARTLLedg-tfkVRVVTRNprkkaa-kelrlqGAEVVQGDQDdq-vIMELALnGAYATFIVTNYwe 90  human
Feature 1                                                                             ###     
2JL1_A     79 d----ntLLIVQHANVVKAARDAGv--KHIAYTGYafaee----siipLAHVHLATEYAIRTTnipYTFLRNALYTDFFv 148 Citrobacter sp. MY-5
1K6I_A     86 ------gDEIAIGKDLADAAKRAGtiqHYIYSSMPdhslyg-pwpavpMWAPKFTVENYVRQLglpSTFVYAGIYNNNFt 158 Emericella nidulans
YP_625387  76 dpapgfpEARKVIEAVSAALLKARp--DRVVCLSTigaqa----depnLLTQLALMEQALREMpmpVTFLRPGWFMENAa 149 Burkholderia cenoc...
2EXX_A     91 sc--sqeQEVKQGKLLADLARRLGl-hYVVYSGLEnikkltagrlaaaHFDGKGEVEEYFRDIgvpMTSVRLPCYFENLl 167 human
Feature 1                                                                                     
2JL1_A    149 neglr------astesGAIVTna-gSGIVNSVTr-nELALAAATVLTeeg--heNKTYNLvsnQPWTfdELAQILSEVSG 218 Citrobacter sp. MY-5
1K6I_A    159 slpyplfqmelmpdgtFEWHApfdpDIPLPWLDaehDVGPALLQIFKdgpqkwnGHRIALt-fETLSpvQVCAAFSRALN 237 Emericella nidulans
YP_625387 150 wdvas-----ardegvVASYLqp-lDKPVPMVAt-aDVGRVAAQLLQqtw--hgVRVVELegpCRVSpnDLALAFARVLG 220 Burkholderia cenoc...
2EXX_A    168 shflpq---kapdgksYLLSLpt-gDVPMDGMSv-sDLGPVVLSLLKmpe-kyvGQNIGLs-tCRHTaeEYAALLTKHTR 240 human
Feature 1             
2JL1_A    219 kKVVHQPV 226 Citrobacter sp. MY-5
1K6I_A    238 rRVTYVQV 245 Emericella nidulans
YP_625387 221 rDVRAEAV 228 Burkholderia cenocepacia AU 1054
2EXX_A    241 kVVHDAKM 248 human

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