4AR1

Crystal Structure of the Peptidase Domain of Collagenase H from Clostridium histolyticum at 2.01 Angstrom resolution.

Summary for 4AR1

• Entry DOI: 10.2210/pdb4ar1/pdb
• Descriptor: COLH PROTEIN, ZINC ION, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: hydrolase, collagen, collagenolysis, peptidase m9, bacterial peptidase
• Biological source: CLOSTRIDIUM HISTOLYTICUM
• Total number of polymer chains: 1
• Total formula weight: 45982.31

Authors

Eckhard, U.,Brandstetter, H. (deposition date: 2012-04-20, release date: 2013-06-05, Last modification date: 2023-12-20)

Primary citation

Eckhard, U.,Schonauer, E.,Brandstetter, H.
Structural Basis for Activity Regulation and Substrate Preference of Clostridial Collagenases G, H, and T.
J.Biol.Chem., 288:20184-, 2013

PubMed Abstract: Clostridial collagenases are among the most efficient enzymes to degrade by far the most predominant protein in the biosphere. Here we present crystal structures of the peptidases of three clostridial collagenase isoforms (ColG, ColH, and ColT). The comparison of unliganded and liganded structures reveals a quaternary subdomain dynamics. In the unliganded ColH structure, this globular dynamics is modulated by an aspartate switch motion that binds to the catalytic zinc. We further identified a calcium binding site in proximity to the catalytic zinc. Both ions are required for full activity, explaining why calcium critically affects the enzymatic activity of clostridial collagenases. Our studies further reveal that loops close to the active site thus serve as characteristic substrate selectivity filter. These elements explain the distinct peptidolytic and collagenolytic activities of these enzymes and provide a rational framework to engineer collagenases with customized substrate specificity as well as for inhibitor design.

PubMed: 23703618
DOI: 10.1074/JBC.M112.448548

Experimental method

X-RAY DIFFRACTION (2.01 Å)