1zdp
From Proteopedia
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Crystal Structure Analysis of Thermolysin Complexed with the Inhibitor (S)-thiorphan
Overview
The three-dimensional structures of (S)-thiorphan and (R)-retro-thiorphan, bound to thermolysin have been determined crystallographically and refined, to residuals of 0.183 and 0.187 at 1.7-A resolution. Thiorphan, [N-[(S)-2-(mercaptomethyl)-1-oxo-3-phenylpropyl]glycine], [HSCH2CH(CH2C6H5)CONHC-H2COOH] and retro-thiorphan, [[[(R)-1-(mercaptomethyl)-2-phenylethyl] amino]-3-oxopropanoic acid], [HSCH2CH(CH2C6H5)NHCOCH2COOH] are isomeric thiol-containing inhibitors of, endopeptidase EC 24-11 (also called "enkephalinase"). The mode of binding, of thiorphan to thermolysin is similar to that of, (2-benzyl-3-mercaptopropanoyl)-L-alanylglycinamide [Monzingo, A.F., &, Matthews, B.W. (1982) Biochemistry 21, 3390-3394] with the inhibitor, sulfur atom coordinated to the active site zinc and the peptide portion, forming substrate-like interactions with the enzyme. The isomeric, inhibitor retro-thiorphan, which differs from thiorphan by the inversion, of an amide bond, utilizes very similar interactions with enzyme. Despite, the inversion of the -CO-NH- linkage the carbonyl oxygen and amide, nitrogen display very similar hydrogen bonding, as anticipated by B.P., Roques et al. [(1983) Proc. Natl. Acad. Sci. U.S.A. 80, 3178-3182]. These, results explain why thermolysin and possibly other zinc endopeptidases, such as endopeptidase EC 24-11 fail to discriminate between these, retro-inverso inhibitors.
About this Structure
1ZDP is a Single protein structure of sequence from Bacillus thermoproteolyticus with CA, ZN and TIO as ligands. Active as Thermolysin, with EC number 3.4.24.27 Full crystallographic information is available from OCA.
Reference
Thiorphan and retro-thiorphan display equivalent interactions when bound to crystalline thermolysin., Roderick SL, Fournie-Zaluski MC, Roques BP, Matthews BW, Biochemistry. 1989 Feb 21;28(4):1493-7. PMID:2719912
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