Myroilysin Is a New Bacterial Member of the M12A Family of Metzincin Metallopeptidases and Is Activated by a Cysteine Switch Mechanism

doi:10.1074/jbc.M116.758110

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	Myroilysin Is a New Bacterial Member of the M12A Family of Metzincin Metallopeptidases and Is Activated by a Cysteine Switch Mechanism
	Xu, DQ; Zhou, JL; Lou, XD; He, JH; Ran, TT; Wang, WW
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2017
卷号	292 期号:13 页码:5195-5206
ISSN号	0021-9258
DOI	10.1074/jbc.M116.758110
文献子类	期刊论文
英文摘要	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, whereas the classification of myroilysin is still unclear 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 propeptide 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, whereas other reported M12A family proteases use an "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 the M12A family and may suggest a divergent evolution of the M12 family.
语种	英语
WOS记录号	WOS:000397875500004
内容类型	期刊论文
源URL	[http://ir.sinap.ac.cn/handle/331007/27390]
专题	上海应用物理研究所_中科院上海应用物理研究所2011-2017年
推荐引用方式 GB/T 7714	Xu, DQ,Zhou, JL,Lou, XD,et al. Myroilysin Is a New Bacterial Member of the M12A Family of Metzincin Metallopeptidases and Is Activated by a Cysteine Switch Mechanism[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2017,292(13):5195-5206.
APA	Xu, DQ,Zhou, JL,Lou, XD,He, JH,Ran, TT,&Wang, WW.(2017).Myroilysin Is a New Bacterial Member of the M12A Family of Metzincin Metallopeptidases and Is Activated by a Cysteine Switch Mechanism.JOURNAL OF BIOLOGICAL CHEMISTRY,292(13),5195-5206.
MLA	Xu, DQ,et al."Myroilysin Is a New Bacterial Member of the M12A Family of Metzincin Metallopeptidases and Is Activated by a Cysteine Switch Mechanism".JOURNAL OF BIOLOGICAL CHEMISTRY 292.13(2017):5195-5206.