9CQE

CRYSTAL STRUCTURE OF APO C-TERMINAL HIS-TAG DOG HSP47(36-418) IN A P 1 21 1 CRYSTAL FORM

This is a non-PDB format compatible entry.

Summary for 9CQE

• Entry DOI: 10.2210/pdb9cqe/pdb
• Descriptor: Serpin H1 (1 entity in total)
• Functional Keywords: chaperone, serpin h1
• Biological source: Canis lupus familiaris (dog)
• Total number of polymer chains: 8
• Total formula weight: 354269.44

Authors

Sheriff, S. (deposition date: 2024-07-19, release date: 2024-10-30, Last modification date: 2024-11-20)

Primary citation

Kish, K.,Cobell, S.,Szapiel, N.,Yan, C.,Newitt, J.A.,Tredup, J.,Rodrigo, I.,Tomasco, E.,Gao, M.,Marsilio, F.,Haugner, J.,Lipovsek, D.,Deng, B.,Bousquet, P.,Zhang, Y.,Schmidt, H.,Sheriff, S.
Improving the diffraction quality of heat-shock protein 47 crystals.
Acta Crystallogr.,Sect.F, 80:302-313, 2024

PubMed Abstract: Heat-shock protein 47 (HSP47) is a potential target for inhibitors that ameliorate fibrosis by reducing collagen assembly. In an effort to develop a structure-based drug-design system, it was not possible to replicate a previous literature result (PDB entry 4au4) for apo dog HSP47; instead, crystal forms were obtained in which pairs of dog HSP47 molecules interacted through a noncleavable C-terminal His-tag to build up tetramers, all of which had multiple molecules of HSP47 in the asymmetric unit and none of which diffracted as well as the literature precedent. To overcome these difficulties, a two-pronged approach was followed: (i) the His-tag was moved from the C-terminus to the N-terminus and was made cleavable, and (ii) Adnectin (derived from the tenth domain of human fibronectin type III) crystallization chaperones were developed. Both approaches provided well diffracting crystals, but the latter approach yielded crystal forms with only one or two HSP47 complexes per asymmetric unit, which made model building less onerous.

PubMed: 39397789
DOI: 10.1107/S2053230X24009233

Experimental method

X-RAY DIFFRACTION (3.177 Å)