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| {{STRUCTURE_1zdp| PDB=1zdp | SCENE= }} | | {{STRUCTURE_1zdp| PDB=1zdp | SCENE= }} |
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| '''Crystal Structure Analysis of Thermolysin Complexed with the Inhibitor (S)-thiorphan'''
| | ===Crystal Structure Analysis of Thermolysin Complexed with the Inhibitor (S)-thiorphan=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_2719912}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 2719912 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_2719912}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Thermostable]] | | [[Category: Thermostable]] |
| [[Category: Zinc endopeptidase]] | | [[Category: Zinc endopeptidase]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 17:30:09 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 06:00:52 2008'' |