PDBsum entry 5czw

Hydrolase

PDB id: 5czw

Contents

Protein chain

229 a.a.

Metals

_ZN

Waters ×214

PDB id:

5czw

Name:

Hydrolase

Title:

Crystal structure of myroilysin

Structure:

Myroilysin. Chain: a. Fragment: unp residues 35-272. Engineered: yes

Source:

Myroides profundi. Organism_taxid: 480520. Gene: mpr_2201. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.60Å R-factor: 0.203 R-free: 0.254

Authors:

J.Zhou,T.Ran,D.Xu,W.Wang

Key ref:

D.Xu et al. (2017). Myroilysin Is a New Bacterial Member of the M12A Family of Metzincin Metallopeptidases and Is Activated by a Cysteine Switch Mechanism. J Biol Chem, 292, 5195-5206. PubMed id: 28188295 DOI: 10.1074/jbc.M116.758110

Date:

01-Aug-15 Release date: 03-Aug-16

Protein chain

B5B0E6  (B5B0E6_9FLAO) -  Astacin (Peptidase family M12A) from Myroides profundi

Seq: 273 a.a.

Struc: 229 a.a.*

* PDB and UniProt seqs differ at 6 residue positions (black crosses)

DOI no: 10.1074/jbc.M116.758110

J Biol Chem 292:5195-5206 (2017)

PubMed id: 28188295

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

D.Xu, J.Zhou, X.Lou, J.He, T.Ran, W.Wang.

ABSTRACT

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 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, 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.