1q5m
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(New page: 200px<br /><applet load="1q5m" size="450" color="white" frame="true" align="right" spinBox="true" caption="1q5m, resolution 1.32Å" /> '''Binary complex of ra...)
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Revision as of 22:16, 20 November 2007
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Binary complex of rabbit 20alpha-hydroxysteroid dehydrogenase with NADPH
Overview
The aldo-keto reductase rabbit 20alpha-hydroxysteroid dehydrogenase, (rb20alpha-HSD; AKR1C5) is less selective than other HSDs, since it exerts, its activity both on androgens (C19 steroids) and progestins (C21, steroids). In order to identify the molecular determinants responsible for, this reduced selectivity, binary (NADPH) and ternary, (NADP(+)/testosterone) complex structures were solved to 1.32A and 2.08A, resolution, respectively. Inspection of the cofactor-binding cavity led to, the identification of a new interaction between side-chains of residues, His222 and Lys270, which cover the central phosphate chain of the, cofactor, reminiscent of the "safety-belt" found in other aldo-keto, reductases. Testosterone is stabilized by a phenol/benzene tunnel composed, of side-chains of numerous residues, among which Phe54, which forces the, steroid to take up an orientation markedly contrasting with that found in, HSD ternary complexes reported. Combining structural, site-directed, mutagenesis, kinetic and fluorescence titration studies, we found that the, selectivity of rb20alpha-HSD is mediated by (i) the relaxation of loop B, (residues 223-230), partly controlled by the nature of residue 230, (ii), the nature of the residue found at position 54, and (iii) the residues, found in the C-terminal tail of the protein especially the side-chain of, the amino acid 306.
About this Structure
1Q5M is a Single protein structure of sequence from Oryctolagus cuniculus with SO4 and NAP as ligands. Full crystallographic information is available from OCA.
Reference
Loop relaxation, a mechanism that explains the reduced specificity of rabbit 20alpha-hydroxysteroid dehydrogenase, a member of the aldo-keto reductase superfamily., Couture JF, Legrand P, Cantin L, Labrie F, Luu-The V, Breton R, J Mol Biol. 2004 May 21;339(1):89-102. PMID:15123423
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