SEQUENCE AND STRUCTURE COMPARISON SUGGEST THAT METHIONINE AMINOPEPTIDASE, PROLIDASE, AMINOPEPTIDASE-P, AND CREATINASE SHARE A COMMON FOLD

Amino acid sequence comparison suggests that the structure of Escheric hia coli methionine aminopeptidase (EC 3.4.11.18) and the C-terminal d omain of Pseudomonas putida creatinase (EC 3.5.3.3) are related. A det ailed comparison of the three-dimensional folds of the two enzymes con firms this homology: within an almost-equal-to 260-residue chain segme nt, 218 C(alpha) atoms of the structures superimpose within 2.5 angstr om; only 41 of these overlapping positions (i.e., 19%) feature identic al amino acids in the two protein chains. Notwithstanding this strikin g correspondence in structure, methionine aminopeptidase binds and is stimulated by Co2+, while creatinase is not a metal-dependent enzyme. Searches of protein data banks using sequence and structure-based prof iles reveal other enzymes, including aminopeptidase P (EC 3.4.11.9), p rolidase (EC 3.4.13.9), and agropine synthase, that likely share the s ame ''pita-bread'' fold common to creatinase and methionine aminopepti dase.