4ZYB

High resolution structure of M23 peptidase LytM with substrate analogue

Summary for 4ZYB

• Entry DOI: 10.2210/pdb4zyb/pdb
• Related: 1QWY 1R77 2B0P 2B13 2B44 3IT5 3IT7 4BH5 4LXC 4QP5 4QPB
• Descriptor: Glycyl-glycine endopeptidase LytM, ZINC ION, CALCIUM ION, ... (10 entities in total)
• Functional Keywords: lytm, lysostaphin, peptidoglycan amidase, peptidase, hydrolase, tetraglycine phosphinate, transition state analogue, complex
• Biological source: Staphylococcus aureus subsp. aureus NCTC 8325
• Cellular location: Secreted : Q6GCJ6
• Total number of polymer chains: 4
• Total formula weight: 61067.16

Authors

Grabowska, M.,Jagielska, E.,Czapinska, H.,Bochtler, M.,Sabala, I. (deposition date: 2015-05-21, release date: 2015-10-21, Last modification date: 2024-01-10)

Primary citation

Grabowska, M.,Jagielska, E.,Czapinska, H.,Bochtler, M.,Sabala, I.
High resolution structure of an M23 peptidase with a substrate analogue.
Sci Rep, 5:14833-14833, 2015

PubMed Abstract: 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.

PubMed: 26437833
DOI: 10.1038/srep14833

Experimental method

X-RAY DIFFRACTION (1.5 Å)