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Publication Abstract from PubMed

Proteases play important roles in all living organisms and also have important industrial applications. Family M12A metalloproteases, mainly found throughout the animal kingdom, belong to the metzincin protease family and are synthesized as inactive precursors. So far, only flavastacin and myroilysin, isolated from bacteria, were reported to be M12A proteases, whilst the classification of myroilysin is still conflicting due to the lack of structural information. Here, we report the crystal structures of pro-myroilysin from bacterium Myroides sp. cslb8. The catalytic zinc ion of pro-myroilysin, at the bottom of a deep active site, is coordinated by three histidine residues in the conserved motif HEXXHXXGXXH; the cysteine residue in the pro-peptide coordinates the catalytic zinc ion and inhibits myroilysin activity. Structure comparisons revealed that myroilysin shares high similarity with the members of the M12A, M10A and M10B families of metalloproteases. However, a unique cap structure tops the active site cleft in the structure of pro-myroilysin, and this cap structure does not exist in the above structure-reported subfamilies. Further structure-based sequence analysis revealed that myroilysin appears to belong to the M12A family, but pro-myroilysin uses a cysteine-switch activation mechanism with a unique segment including the conserved cysteine residue while other reported M12A family proteases use aspartate-switch activation mechanism. Thus, our results suggest that myroilysin is a new bacterial member of the M12A family with an exceptional cysteine-switch activation mechanism. Our results shed new light on the classification of M12A family, and may suggest a divergent evolution of M12 family.

Myroilysin is a New Bacterial Member of the M12A Family of Metzincin Metallopeptidases and Activated by a Cysteine-switch Mechanism.,Xu D, Zhou J, Lou X, He J, Ran T, Wang W J Biol Chem. 2017 Feb 9. pii: jbc.M116.758110. doi: 10.1074/jbc.M116.758110. PMID:28188295^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.