Binding of a reduced peptide inhibitor to the aspartic proteinase from Rhizopus chinensis: implications for a mechanism of action

Journal Article · Thu Oct 01 00:00:00 EDT 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.20.7009· OSTI ID:6993495

Suguna, K; Padlan, E A; Smith, C W; Carlson, W D; Davies, D R

A peptide inhibitor, having the sequence D-His-Pro-Phe-His-PhePsi(CH/sub 2/-NH)Phe-Val-Tyr, with a reduced bond between the two adjacent phenylalanines, has been diffused into crystals of the aspartic proteinase from Rhizopus chinensis. X-ray diffraction data to 1.8-A resolution have been collected on the complex, which has been subjected to restrained least-squares refinement to an R-factor of 14.7%. The inhibitor lies within the major groove of the enzyme and is clearly defined with the exception of the amino-terminal D-histidine and the carboxyl-terminal tyrosine. The reduced peptide bond is located in the active site with close contacts to the two catalytic aspartyl groups. The active-site water molecule that is held between the two carboxyl groups is displaced by the inhibitor, as are a number of other water molecules seen in the binding groove of the native enzyme. A mechanism of action for this class of enzymes is proposed from these results.

• Research Organization: National Institutes of Health, Bethesda, MD (USA)
• OSTI ID: 6993495
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 84:20
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
ENZYME INHIBITORS
CONFIGURATION INTERACTION
X-RAY DIFFRACTION
PEPTIDE HYDROLASES
CHEMICAL BONDS
PHENYLALANINE
RHIZOPUS
STEREOCHEMISTRY
AMINO ACIDS
CARBOXYLIC ACIDS
COHERENT SCATTERING
DIFFRACTION
ENZYMES
FUNGI
HYDROLASES
ORGANIC ACIDS
ORGANIC COMPOUNDS
PLANTS
SCATTERING
550602* - Medicine- External Radiation in Diagnostics- (1980-)