4JRW

Crystal structure of Clostridium histolyticum colg collagenase PKD domain 2 at 1.6 Angstrom resolution

Replaces:  3JS7

Summary for 4JRW

• Entry DOI: 10.2210/pdb4jrw/pdb
• Related: 2C4X 2Y72 3JQU 3JQW 4HPK 4JGU
• Descriptor: Collagenase, BROMIDE ION (3 entities in total)
• Functional Keywords: ig-like fold, beta-sandwich, cell adhesion
• Biological source: Clostridium histolyticum
• Total number of polymer chains: 2
• Total formula weight: 18425.89

Authors

Sakon, J.,Philominathan, S.T.L.,Gann, S.,Bauer, R.,Matsushita, O. (deposition date: 2013-03-22, release date: 2014-05-21, Last modification date: 2023-09-20)

Primary citation

Bauer, R.,Janowska, K.,Taylor, K.,Jordan, B.,Gann, S.,Janowski, T.,Latimer, E.C.,Matsushita, O.,Sakon, J.
Structures of three polycystic kidney disease-like domains from Clostridium histolyticum collagenases ColG and ColH.
Acta Crystallogr.,Sect.D, 71:565-577, 2015

PubMed Abstract: Clostridium histolyticum collagenases ColG and ColH are segmental enzymes that are thought to be activated by Ca(2+)-triggered domain reorientation to cause extensive tissue destruction. The collagenases consist of a collagenase module (s1), a variable number of polycystic kidney disease-like (PKD-like) domains (s2a and s2b in ColH and s2 in ColG) and a variable number of collagen-binding domains (s3 in ColH and s3a and s3b in ColG). The X-ray crystal structures of Ca(2+)-bound holo s2b (1.4 Å resolution, R = 15.0%, Rfree = 19.1%) and holo s2a (1.9 Å resolution, R = 16.3%, Rfree = 20.7%), as well as of Ca(2+)-free apo s2a (1.8 Å resolution, R = 20.7%, Rfree = 27.2%) and two new forms of N-terminally truncated apo s2 (1.4 Å resolution, R = 16.9%, Rfree = 21.2%; 1.6 Å resolution, R = 16.2%, Rfree = 19.2%), are reported. The structurally similar PKD-like domains resemble the V-set Ig fold. In addition to a conserved β-bulge, the PKD-like domains feature a second bulge that also changes the allegiance of the subsequent β-strand. This β-bulge and the genesis of a Ca(2+) pocket in the archaeal PKD-like domain suggest a close kinship between bacterial and archaeal PKD-like domains. Different surface properties and indications of different dynamics suggest unique roles for the PKD-like domains in ColG and in ColH. Surface aromatic residues found on ColH s2a-s2b, but not on ColG s2, may provide the weak interaction in the biphasic collagen-binding mode previously found in s2b-s3. B-factor analyses suggest that in the presence of Ca(2+) the midsection of s2 becomes more flexible but the midsections of s2a and s2b stay rigid. The different surface properties and dynamics of the domains suggest that the PKD-like domains of M9B bacterial collagenase can be grouped into either a ColG subset or a ColH subset. The conserved properties of PKD-like domains in ColG and in ColH include Ca(2+) binding. Conserved residues not only interact with Ca(2+), but also position the Ca(2+)-interacting water molecule. Ca(2+) aligns the N-terminal linker approximately parallel to the major axis of the domain. Ca(2+) binding also increases stability against heat and guanidine hydrochloride, and may improve the longevity in the extracellular matrix. The results of this study will further assist in developing collagen-targeting vehicles for various signal molecules.

PubMed: 25760606
DOI: 10.1107/S1399004714027722

Experimental method

X-RAY DIFFRACTION (1.6 Å)