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High resolution structure of an M23 peptidase with a substrate analogue

Grabowska, Maja and Jagielska, Elzbieta and Czapinska, Honorata and Bochtler, Matthias and Sabala, Izabela (2015) High resolution structure of an M23 peptidase with a substrate analogue. Scientific Reports, 5 (14833). pp. 1-8.


Official URL: http://www.nature.com/articles/srep14833


LytM is a Staphylococcus aureus autolysin and a homologue of the S. simulans lysostaphin. Both enzymes are members of M23 metallopeptidase family (MEROPS) comprising primarily bacterial peptidoglycan hydrolases. LytM occurs naturally in a latent form, but can be activated by cleavage of an inhibitory N-terminal proregion. Here, we present a 1.45 Å crystal structure of LytM catalytic domain with a transition state analogue, tetraglycine phosphinate, bound in the active site. In the electron density, the active site of the peptidase, the phosphinate and the "diglycine" fragment on the P1' side of the transition state analogue are very well defined. The density is much poorer or even absent for the P1 side of the ligand. The structure is consistent with the involvement of His260 and/or His291 in the activation of the water nucleophile and suggests a possible catalytic role for Tyr204, which we confirmed by mutagenesis. Possible mechanisms of catalysis and the structural basis of substrate specificity are discussed based on the structure analysis.

Item Type:Article
Subjects:Q Science > Q Science (General)
Divisions:Department of Bioinformatics
ID Code:1096
Deposited By: Prof. Matthias Bochtler
Deposited On:22 Dec 2015 13:04
Last Modified:08 Jan 2016 08:23

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