4ARF: CRYSTAL STRUCTURE OF THE PEPTIDASE DOMAIN OF COLLAGENASE H FROM CLOSTRIDIUM HISTOLYTICUM IN COMPLEX WITH THE PEPTIDIC INHIBITOR ISOAMYLPHOSPHONYL-GLY-PRO-ALA AT 1.77 ANGSTROM RESOLUTION

Citation:
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.
PDB ID: 4ARFDownload
MMDB ID: 159233
PDB Deposition Date: 2012/4/23
Updated in MMDB: 2018/02
Experimental Method:
x-ray diffraction
Resolution: 1.77  Å
Source Organism:
Hathewaya histolytica
Similar Structures:
Biological Unit for 4ARF: tetrameric; determined by author and by software (PISA)
Molecular Components in 4ARF
Label Count Molecule
Proteins (4 molecules)
2
Colh Protein
Molecule annotation
2
Isoamylphosphonyl-gly-pro-ala
Molecule annotation
Chemicals (4 molecules)
1
2
2
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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