3NQY

Crystal structure of the autoprocessed complex of Vibriolysin MCP-02 with a single point mutation E346A

Summary for 3NQY

• Entry DOI: 10.2210/pdb3nqy/pdb
• Related: 3NQX 3NQZ
• Descriptor: Secreted metalloprotease Mcp02, CALCIUM ION, ZINC ION, ... (5 entities in total)
• Functional Keywords: autoprocessed complex, propeptide, thermolysin-like protease, hydrolase
• Biological source: Pseudoalteromonas sp.; More
• Total number of polymer chains: 2
• Total formula weight: 53795.59

Authors

Gao, X.,Wang, J.,Wu, J.-W.,Zhang, Y.-Z. (deposition date: 2010-06-30, release date: 2010-10-06, Last modification date: 2024-11-06)

Primary citation

Gao, X.,Wang, J.,Yu, D.-Q.,Bian, F.,Xie, B.-B.,Chen, X.-L.,Zhou, B.-C.,Lai, L.-H.,Wang, Z.-X.,Wu, J.-W.,Zhang, Y.-Z.
Structural basis for the autoprocessing of zinc metalloproteases in the thermolysin family
Proc.Natl.Acad.Sci.USA, 107:17569-17574, 2010

PubMed Abstract: Thermolysin-like proteases (TLPs), a large group of zinc metalloproteases, are synthesized as inactive precursors. TLPs with a long propeptide (∼200 residues) undergo maturation following autoprocessing through an elusive molecular mechanism. We report the first two crystal structures for the autoprocessed complexes of a typical TLP, MCP-02. In the autoprocessed complex, Ala205 shifts upward by 33 Å from the previously covalently linked residue, His204, indicating that, following autocleavage of the peptide bond between His204 and Ala205, a large conformational change from the zymogen to the autoprocessed complex occurs. The eight N-terminal residues (residues Ala205-Gly212) of the catalytic domain form a new β-strand, nestling into two other β-strands. Simultaneously, the apparent T(m) of the autoprocessed complex increases 20 °C compared to that of the zymogen. The stepwise degradation of the propeptide begins with two sequential cuttings at Ser49-Val50 and Gly57-Leu58, which lead to the disassembly of the propeptide and the formation of mature MCP-02. Our findings give new insights into the molecular mechanism of TLP maturation.

PubMed: 20876133
DOI: 10.1073/pnas.1005681107

Experimental method

X-RAY DIFFRACTION (2.6 Å)