ISSN:
0020-7608
Keywords:
leupeptin
;
papain
;
semiempirical
;
cysteine protease
;
active center
;
Chemistry
;
Theoretical, Physical and Computational Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
In this work, we modeled leupeptin (Ac.Leu.Leu.Arg.CHO), a natural inhibitor of proteases, and the active site of papain, a cysteine protease, using as a template the crystal structure of a leupeptin-papain complex recently obtained by Schroder and co-workers [FEBS Lett. 135(1), 38 (1993)] and including 11 amino acids relevant to the proteolytic activity of the enzyme. Our results show that the AM1 fully optimized leupeptin is more stable than is the leupeptin crystal structure by about 6.0 kcal/mol. Our results show also that in the modeled active center of papain the S - H⋅⋅⋅N structure is favored. When the aldehyde is included in the calculation, however, proton transfer occurs with a strengthening of the S-⋅⋅⋅HIm+⋅⋅⋅O(DOUBLE BOND)C (Asn175) catalytic triad. The AM1 method reproduces fairly well the interactions between the enzyme and the host molecule. © 1997 John Wiley & Sons, Inc. Int J Quant Chem 65: 1125-1134, 1997
Additional Material:
6 Ill.
Type of Medium:
Electronic Resource
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