3APR

BINDING OF A REDUCED PEPTIDE INHIBITOR TO THE ASPARTIC PROTEINASE FROM RHIZOPUS CHINENSIS. IMPLICATIONS FOR A MECHANISM OF ACTION

Summary for 3APR

• Entry DOI: 10.2210/pdb3apr/pdb
• Related PRD ID: PRD_000298
• Descriptor: RHIZOPUSPEPSIN, REDUCED PEPTIDE INHIBITOR (3 entities in total)
• Functional Keywords: hydrolase, aspartic proteinase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Rhizopus microsporus var. chinensis
• Total number of polymer chains: 2
• Total formula weight: 35149.90

Authors

Suguna, K.,Davies, D.R. (deposition date: 1987-06-22, release date: 1988-01-16, Last modification date: 2024-11-13)

Primary citation

Suguna, K.,Padlan, E.A.,Smith, C.W.,Carlson, W.D.,Davies, D.R.
Binding of a reduced peptide inhibitor to the aspartic proteinase from Rhizopus chinensis: implications for a mechanism of action.
Proc.Natl.Acad.Sci.USA, 84:7009-7013, 1987

PubMed Abstract: A peptide inhibitor, having the sequence D-His-Pro-Phe-His-Phe psi [CH2-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 (rhizopuspepsin, EC 3.4.23.6). 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 (R equals the sum of the absolute value of the difference between the observed and calculated structure factor amplitudes divided by the sum of the observed structure factor amplitudes) 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.

PubMed: 3313384
DOI: 10.1073/pnas.84.20.7009

Experimental method

X-RAY DIFFRACTION (1.8 Å)