6XLY

CRYOEM STRUCTURE OF MYCOBACTERIUM TUBERCULOSIS ZINC METALLOPROTEASE ZMP1 IN OPEN STATE

Summary for 6XLY

• Entry DOI: 10.2210/pdb6xly/pdb
• EMDB information: 22252
• Descriptor: Probable zinc metalloprotease Zmp1, ZINC ION (2 entities in total)
• Functional Keywords: open state, hydrolase
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• Total number of polymer chains: 1
• Total formula weight: 78198.36

Authors

Liang, W.G.,Zhao, M.,Tang, W. (deposition date: 2020-06-29, release date: 2020-12-23, Last modification date: 2024-03-06)

Primary citation

Liang, W.G.,Mancl, J.M.,Zhao, M.,Tang, W.J.
Structural analysis of Mycobacterium tuberculosis M13 metalloprotease Zmp1 open states.
Structure, 29:709-, 2021

PubMed Abstract: Zinc metalloprotease 1 (Zmp1), a Mycobacterium tuberculosis 75 kDa secreted enzyme, mediates key stages of tuberculosis disease progression. The biological activity of Zmp1 presumably stems from its ability to degrade bacterium- and/or host-derived peptides. The crystal structures of Zmp1 and related M13 metalloproteases, such as neprilysin and endothelin-converting enzyme-1 were determined only in the closed conformation, which cannot capture substrates or release proteolytic products. Thus, the mechanisms of substrate binding and selectivity remain elusive. Here we report two open-state cryo-EM structures of Zmp1, revealed by our SAXS analysis to be the dominant states in solution. Our structural analyses reveal how ligand binding induces a conformational switch in four linker regions to drive the rigid body motion of the D1 and D2 domains, which form the sizable catalytic chamber. Furthermore, they offer insights into the catalytic cycle and mechanism of substrate recognition of M13 metalloproteases for future therapeutic innovations.

PubMed: 33378640
DOI: 10.1016/j.str.2020.12.002

Experimental method

ELECTRON MICROSCOPY (3.1 Å)