Sequence and Structure Comparison Suggest that Methionine Aminopeptidase, Prolidase, Aminopeptidase P, and Creatinase Share a Common Fold

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 7; pp. 2473 - 2477
• Main Authors: Bazan, J. F., Weaver, L. H., Roderick, S. L., Huber, R., Matthews, B. W.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 29.03.1994; National Acad Sciences; National Academy of Sciences
• Subjects: Active sites; Amino Acid Sequence; Amino acids; Aminopeptidases - chemistry; Analytical, structural and metabolic biochemistry; Atoms; Bacteriology; Biochemistry; Biological and medical sciences; Cobalt; Creatine; Dipeptidases - chemistry; Enzymes; 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; Proteins; Pseudomonas putida; Pseudomonas putida - enzymology; Sequence alignment; Sequence Homology, Amino Acid; Ureohydrolases - chemistry; Enzyme; Aminopeptidases; Interspecific comparison; Escherichia coli; Sequence alignment; Dipeptidases; X-Pro dipeptidase; Creatinase; Bacteria; Hydrolases; X-Pro aminopeptidase; Proteinases; Aminoacid sequence; Enterobacteriaceae; Structural analysis; Methionyl aminopeptidase
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.7.2473

Amino acid sequence comparison suggests that the structure of Escherichia coli methionine aminopeptidase (EC 3.4.11.18) and the C-terminal domain of Pseudomonas putida creatinase (EC 3.5.3.3) are related. A detailed comparison of the three-dimensional folds of the two enzymes confirms this homology: within an ≈260-residue chain segment, 218 Cαatoms of the structures superimpose within 2.5 Å; only 41 of these overlapping positions (i.e., 19%) feature identical amino acids in the two protein chains. Notwithstanding this striking 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 profiles reveal other enzymes, including aminopeptidase P (EC 3.4.11.9), prolidase (EC 3.4.13.9), and agropine synthase, that likely share the same "pita-bread" fold common to creatinase and methionine aminopeptidase.