The aldo-keto reductase family is a family of proteins that are subdivided into 16 categories; these include a number of related monomeric NADPH-dependent oxidoreductases, such as aldehyde reductase, aldose reductase, prostaglandin F synthase, xylose reductase, rho crystallin, and many others.[1]

Aldo/keto reductase family
Ribbon diagram of human aldose reductase in complex with NADP+, citrate, and IDD594, a small molecule inhibitor. From PDB: 1us0​.
Identifiers
SymbolAldo_ket_red
PfamPF00248
InterProIPR001395
PROSITEPDOC00061
SCOP21ads / SCOPe / SUPFAM
CDDcd06660
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
PDB1a80​, 1abn​, 1ads​, 1ae4​, 1afs​, 1ah0​, 1ah3​, 1ah4​, 1az1​, 1az2​, 1c9w​, 1cwn​, 1dla​, 1ef3​, 1eko​, 1el3​, 1exb​, 1frb​, 1gve​, 1hqt​, 1hw6​, 1iei​, 1ihi​, 1j96​, 1jez​, 1k8c​, 1lqa​, 1lwi​, 1m9h​, 1mar​, 1mi3​, 1mrq​, 1mzr​, 1og6​, 1pwl​, 1pwm​, 1pyf​, 1pz0​, 1pz1​, 1q13​, 1q5m​, 1qrq​, 1qwk​, 1r38​, 1ral​, 1ry0​, 1ry8​, 1s1p​, 1s1r​, 1s2a​, 1s2c​, 1sm9​, 1t40​, 1t41​, 1ur3​, 1us0​, 1vbj​, 1vp5​, 1x96​, 1x97​, 1x98​, 1xf0​, 1xgd​, 1xjb​, 1ye4​, 1ye6​, 1z3n​, 1z89​, 1z8a​, 1z9a​, 1zgd​, 1zq5​, 1zsx​, 2a79​, 2acq​, 2acr​, 2acs​, 2acu​, 2agt​, 2alr​, 2bgq​, 2bgs​, 2bp1​, 2c91​, 2clp​, 2dux​, 2duz​, 2dv0​, 2f2k​, 2f38​, 2fgb​, 2fvl​, 2fz8​, 2fz9​, 2fzb​, 2fzd​, 2hdj​, 2he5​, 2he8​, 2hej​, 2hv5​, 2hvn​, 2hvo​, 2i16​, 2i17​, 2ikg​, 2ikh​, 2iki​, 2ikj​, 2ine​, 2inz​, 2ipf​, 2ipg​, 2ipj​, 2ipw​, 2iq0​, 2iqd​, 2is7​, 2isf​, 2j8t​, 2nvc​, 2nvd​, 2p5n​, 2pd5​, 2pd9​, 2pdb​, 2pdc​, 2pdf​, 2pdg​, 2pdh​, 2pdi​, 2pdj​, 2pdk​, 2pdl​, 2pdm​, 2pdn​, 2pdp​, 2pdq​, 2pdu​, 2pdw​, 2pdx​, 2pdy​, 2pev​, 2pf8​, 2pfh​, 2pzn​, 2qxw​, 2r9r​, 2vdg​, 3bcj​, 3bur​, 3buv​, 3bv7​, 3c3u​, 3cmf​, 3cot​, 3eau

Structure

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All possess a similar structure, with a beta-alpha-beta fold characteristic of nucleotide binding proteins.[2] The fold comprises a parallel beta-8/alpha-8-barrel, which contains a novel NADP-binding motif. The binding site is located in a large, deep, elliptical pocket in the C-terminal end of the beta sheet, the substrate being bound in an extended conformation. The hydrophobic nature of the pocket favours aromatic and apolar substrates over highly polar ones.[3]

Binding of the NADPH coenzyme causes a massive conformational change, reorienting a loop, effectively locking the coenzyme in place. This binding is more similar to FAD- than to NAD(P)-binding oxidoreductases.[4]

Examples

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Some proteins of this family contain a potassium channel beta chain regulatory domain; these are reported to have oxidoreductase activity.[5]

See also

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References

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  1. ^ Bohren KM, Bullock B, Wermuth B, Gabbay KH (June 1989). "The aldo-keto reductase superfamily. cDNAs and deduced amino acid sequences of human aldehyde and aldose reductases". J. Biol. Chem. 264 (16): 9547–51. doi:10.1016/S0021-9258(18)60566-6. PMID 2498333.
  2. ^ Schade SZ, Early SL, Williams TR, Kézdy FJ, Heinrikson RL, Grimshaw CE, Doughty CC (March 1990). "Sequence analysis of bovine lens aldose reductase". J. Biol. Chem. 265 (7): 3628–35. doi:10.1016/S0021-9258(19)39639-5. PMID 2105951.
  3. ^ Wilson DK, Bohren KM, Gabbay KH, Quiocho FA (July 1992). "An unlikely sugar substrate site in the 1.65 A structure of the human aldose reductase holoenzyme implicated in diabetic complications". Science. 257 (5066): 81–4. doi:10.1126/science.1621098. PMID 1621098.
  4. ^ Borhani DW, Harter TM, Petrash JM (December 1992). "The crystal structure of the aldose reductase.NADPH binary complex". J. Biol. Chem. 267 (34): 24841–7. doi:10.2210/pdb1abn/pdb. PMID 1447221.
  5. ^ Gulbis JM, Zhou M, Mann S, MacKinnon R (July 2000). "Structure of the cytoplasmic beta subunit-T1 assembly of voltage-dependent K+ channels". Science. 289 (5476): 123–7. Bibcode:2000Sci...289..123G. doi:10.1126/science.289.5476.123. PMID 10884227.
This article incorporates text from the public domain Pfam and InterPro: IPR001395