Structure and mechanism of a proline-specific aminopeptidase from Escherichia coli

Matthew Wilce, Charles S. Bond, Nicholas E. Dixon, Hans C. Freeman, Jules Mitchell Guss, Penelope E. Lilley, Jacqueline Anne Wilce

Research output: Contribution to journalArticlepeer-review

167 Citations (Scopus)


The structure of the proline-specific amino-peptidase (EC from Escherichia coli has been solved and refined for crystals of the native enzyme at a 2.0-Å resolution, for a dipeptide-inhibited complex at 2.3-Å resolution, and for a low-pH inactive form at 2.7-Å resolution. The protein crystallizes as a tetramer, more correctly a dimer of dimers, at both high and low pH, consistent with observations from analytical ultracentrifuge studies that show that the protein is a tetramer under physiological conditions. The monomer folds into two domains. The active site, in the larger C-terminal domain, contains a dinuclear manganese center in which a bridging water molecule or hydroxide ion appears poised to act as the nucleophile in the attack on the scissile peptide bond of Xaa-Pro. The metal- binding residues are located in a single subunit, but the residues surrounding the active site are contributed by three subunits. The fold of the protein resembles that of creatine amidinohydrolase (creatinase, not a metalloenzyme). The C-terminal catalytic domain is also similar to the single-domain enzyme methionine aminopeptidase that has a dinuclear cobalt center.

Original languageEnglish
Pages (from-to)3472-3477
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number7
Publication statusPublished - 31 Mar 1998


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