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PDBsum entry 1zdp
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References listed in PDB file
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Key reference
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Title
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Thiorphan and retro-Thiorphan display equivalent interactions when bound to crystalline thermolysin.
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Authors
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S.L.Roderick,
M.C.Fournie-Zaluski,
B.P.Roques,
B.W.Matthews.
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Ref.
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Biochemistry, 1989,
28,
1493-1497.
[DOI no: ]
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PubMed id
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Abstract
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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.
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