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InterPro: IPR018170 Aldo/keto reductase, conserved site
Protein matches
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UniProtKB Matches: 4180 proteins |
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Accession
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IPR018170 Aldo/ket_reductase_CS |
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Type
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Conserved_site |
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Signatures
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InterPro Relationships
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Found in
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IPR001395 Aldo/keto reductase
IPR020471 Aldo/keto reductase subgroup
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GO Term annotation
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Process
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GO:0055114 oxidation reduction
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Function
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GO:0016491 oxidoreductase activity
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InterPro annotation
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 Entry Details in BioMart
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Abstract
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The aldo-keto reductase family includes 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]. 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].
Some proteins of this entry contain a K+ ion channel beta chain regulatory domain; these are reported to have oxidoreductase activity [5].
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Structural links
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Database links
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Publications
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1.
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Bohren KM, Bullock B, Wermuth B, Gabbay KH.
The aldo-keto reductase superfamily. cDNAs and deduced amino acid sequences of human aldehyde and aldose reductases.
J. Biol. Chem. 264 9547-51 1989
[PubMed: 2498333]
http://intl.jbc.org/cgi/reprint/264/16/9547.pdf
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2.
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Schade SZ, Early SL, Williams TR, Kezdy FJ, Heinrikson RL, Grimshaw CE, Doughty CC.
Sequence analysis of bovine lens aldose reductase.
J. Biol. Chem. 265 3628-35 1990
[PubMed: 2105951]
http://intl.jbc.org/cgi/reprint/265/7/3628.pdf
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3.
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Wilson DK, Bohren KM, Gabbay KH, Quiocho FA.
An unlikely sugar substrate site in the 1.65 A structure of the human aldose reductase holoenzyme implicated in diabetic complications.
Science 257 81-4 1992
[PubMed: 1621098]
http://www.sciencemag.org/cgi/content/abstract/257/5066/81
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4.
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Borhani DW, Harter TM, Petrash JM.
The crystal structure of the aldose reductase.NADPH binary complex.
J. Biol. Chem. 267 24841-7 1992
[PubMed: 1447221]
http://intl.jbc.org/cgi/content/abstract/267/34/24841
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5.
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Gulbis JM, Zhou M, Mann S, MacKinnon R.
Structure of the cytoplasmic beta subunit-T1 assembly of voltage-dependent K+ channels.
Science 289 123-7 2000
[PubMed: 10884227]
http://dx.doi.org/10.1126/science.289.5476.123
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Additional Reading
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Bruce NC, Willey DL, Coulson AF, Jeffery J.
Bacterial morphine dehydrogenase further defines a distinct superfamily of oxidoreductases with diverse functional activities.
Biochem. J. 299 ( Pt 3) 1994 805-11
[PubMed: 8192670]
http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=EBI&pubmedid=8192670&action=stream&blobtype=pdf
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Dhagat U, Endo S, Sumii R, Hara A, El-Kabbani O.
Selectivity determinants of inhibitor binding to human 20alpha-hydroxysteroid dehydrogenase: crystal structure of the enzyme in ternary complex with coenzyme and the potent inhibitor 3,5-dichlorosalicylic acid.
J. Med. Chem. 51 2008 4844-8
[PubMed: 18620380]
http://dx.doi.org/10.1021/jm8003575
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Di Costanzo L, Drury JE, Penning TM, Christianson DW.
Crystal structure of human liver Delta4-3-ketosteroid 5beta-reductase (AKR1D1) and implications for substrate binding and catalysis.
J. Biol. Chem. 283 2008 16830-9
[PubMed: 18407998]
http://dx.doi.org/10.1074/jbc.M801778200
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Zhao HT, Hazemann I, Mitschler A, Carbone V, Joachimiak A, Ginell S, Podjarny A, El-Kabbani O.
Unusual binding mode of the 2S4R stereoisomer of the potent aldose reductase cyclic imide inhibitor fidarestat (2S4S) in the 15 K crystal structure of the ternary complex refined at 0.78 A resolution: implications for the inhibition mechanism.
J. Med. Chem. 51 2008 1478-81
[PubMed: 18284183]
http://dx.doi.org/10.1021/jm701514k
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Thorsell AG, Persson C, Voevodskaya N, Busam RD, Hammarstrom M, Graslund S, Graslund A, Hallberg BM.
Structural and biophysical characterization of human myo-inositol oxygenase.
J. Biol. Chem. 283 2008 15209-16
[PubMed: 18364358]
http://dx.doi.org/10.1074/jbc.M800348200
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Olsen JG, Pedersen L, Christensen CL, Olsen O, Henriksen A.
Barley aldose reductase: structure, cofactor binding, and substrate recognition in the aldo/keto reductase 4C family.
Proteins 71 2008 1572-81
[PubMed: 18300247]
http://dx.doi.org/10.1002/prot.21996
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InterPro 23.1
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