Structure of the cobalt-dependent methionine aminopeptidase from Escherichia coli: a new type of proteolytic enzyme

• Published in: Biochemistry (Easton) Vol. 32; no. 15; pp. 3907 - 3912
• Main Authors: Roderick, Steven L, Matthews, Brian W
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 20.04.1993
• Subjects: Amino Acid Sequence; Aminopeptidases - chemistry; Aminopeptidases - isolation & purification; Aminopeptidases - metabolism; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Cobalt - pharmacology; Enzymes and enzyme inhibitors; Escherichia coli; Escherichia coli - enzymology; Fundamental and applied biological sciences. Psychology; Hydrolases; Methionyl Aminopeptidases; Models, Molecular; Molecular Sequence Data; Protein Conformation; Protein Folding; Protein Structure, Secondary; Sequence Homology, Amino Acid; X-Ray Diffraction - methods; Bacteria; Molecular structure; Enzyme; Structure function relationship; Escherichia coli; Enterobacteriaceae
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi00066a009

The X-ray structure of Escherichia coli methionine aminopeptidase (MAP) has been determined to 2.4-A resolution and refined to a crystallographic R-factor of 18.2%. The fold is novel and displays internal pseudo-2-fold symmetry which structurally relates the first and second halves of the polypeptide chain. The topology consists of a central antiparallel beta-sheet covered on one side by two pairs of alpha-helices and by a C-terminal loop. The other face of the beta-sheet, together with some irregular loops, forms the active site, which contains two cobalt ions 2.9 A apart. These metal ions are liganded by the side chains of Asp 97, Asp 108, Glu 204, Glu 235, and His 171 with approximate octahedral coordination. In terms of both the novel backbone fold and the constitution of the active site, MAP appears to represent a new class of proteolytic enzyme.