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Activation and binding mechanisms of the tandem collagen‐binding domain of ColG collagenase
Author(s) -
Bauer Ryan,
Janowska Katarzyna,
Tanaka Keisuke,
Matsushita Osamu,
Sakon Joshua
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb85
Subject(s) - collagenase , extracellular matrix , chemistry , biophysics , tandem repeat , binding site , matrix metalloproteinase , mechanism of action , microbiology and biotechnology , computational biology , biochemistry , enzyme , biology , in vitro , gene , genome
Clinically viable Clostridium histolyticum collagenases, ColG and ColH, contain variable numbers of collagen‐binding domains (CBD) (s3a‐s3b in ColG; s3 in ColH). These segments can be utilized to deliver therapeutics directly to their site of action. Since clinical outcomes depend on which binder is used, understanding the collagen‐binding and activation mechanisms are essential. To help elucidate these mechanisms, the crystal structure of the Ca 2+ ‐bound ColG tandem CBD, has been solved at 1.9 Å resolution. The structure revealed a pseudo‐two fold symmetry arrangement of s3a and s3b that suggests that the domain can bind trans to two collagen molecules. Collagen fiber formation studies further supported this mechanism. Furthermore, it is thought that the difference in Ca 2+ concentrations between the clostridial cell and host extracellular matrix (ECM) can be exploited to facilitate secretion into the ECM and subsequent activation. Structure envelopes derived from small angle X‐ray scattering data of tandem CBD in the presence of different Ca 2+ concentrations showed structural compacting upon increasing Ca 2+ concentrations. Insights gained form this study will help guide therapeutic delivery strategies.