1Z9G

Crystal Structure Analysis of Thermolysin Complexed with the Inhibitor (R)-retro-thiorphan

Summary for 1Z9G

• Entry DOI: 10.2210/pdb1z9g/pdb
• Descriptor: Thermolysin, CALCIUM ION, ZINC ION, ... (5 entities in total)
• Functional Keywords: enzyme-inhibitor complex; zinc endopeptidase; gamma turn; thermostable, hydrolase
• Biological source: Bacillus thermoproteolyticus
• Cellular location: Secreted: P00800
• Total number of polymer chains: 1
• Total formula weight: 34841.34

Authors

Roderick, S.L.,Fournie-Zaluski, M.C.,Roques, B.P.,Matthews, B.W. (deposition date: 2005-04-01, release date: 2005-04-19, Last modification date: 2023-08-23)

Primary citation

Roderick, S.L.,Fournie-Zaluski, M.C.,Roques, B.P.,Matthews, B.W.
Thiorphan and retro-thiorphan display equivalent interactions when bound to crystalline thermolysin
Biochemistry, 28:1493-1497, 1989

PubMed Abstract: 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.

PubMed: 2719912
DOI: 10.1021/bi00430a011

Experimental method

X-RAY DIFFRACTION (1.7 Å)