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Published June 1981 | Published
Journal Article Open

Zinc Environment and cis Peptide Bonds in Carboxypeptidase A at 1.75Å Resolution

Abstract

The structure of the metalloenzyme carboxypeptidase A (peptidyl-L-amino-acid hydrolase, EC 3.4.17.1) has been refined at 1.75 Å by a restrained least-squares procedure to a conventional crystallographic R factor of 0.162. Significant results of the refined structure relative to the catalytic mechanism are described. In the native enzyme, the zinc coordination number is five (two imidazole N delta 1 nitrogens, the two carboxylate oxygens of glutamate-72, and a water molecule). In the complex (at 2.0-Å resolution) of carboxypeptidase A with the dipeptide glycyl-L-tyrosine, however, the water ligand is replaced by both the carbonyl oxygen and the amino nitrogen of the dipeptide. The amino nitrogen also statistically occupies a second position near glutamate-270. Consequently, the coordination number of zinc may vary from five to six in carboxypeptidase A-substrate complexes. Implications of these results for the catalytic mechanism of carboxypeptidase A are discussed. In addition, three cis peptide bonds, none of which involves proline as the amino nitrogen donor, have been located fairly near the active site.

Additional Information

© 1981 National Academy of Sciences. Contributed by William N. Lipscomb, February 27, 1981. We thank R. C. Ladner for his assistance with the graphics programs, the National Institutes of Health (GM 06920) for support of this research, the National Science Foundation (PCM 77-11398) for support of the computational facilities, and the American Cancer Society for a Postdoctoral Fellowship (N.I.L.). The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.

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August 22, 2023
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