3TJQ

N-domain of HtrA1

Summary for 3TJQ

• Entry DOI: 10.2210/pdb3tjq/pdb
• Related: 3TJN 3TJO
• Descriptor: Serine protease HTRA1, PLATINUM (II) ION, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: Q92743
• Total number of polymer chains: 1
• Total formula weight: 15578.78

Authors

Eigenbrot, C.,Ultsch, M. (deposition date: 2011-08-24, release date: 2012-05-16, Last modification date: 2024-10-09)

Primary citation

Eigenbrot, C.,Ultsch, M.,Lipari, M.T.,Moran, P.,Lin, S.J.,Ganesan, R.,Quan, C.,Tom, J.,Sandoval, W.,van Lookeren Campagne, M.,Kirchhofer, D.
Structural and Functional Analysis of HtrA1 and Its Subdomains.
Structure, 20:1040-1050, 2012

PubMed Abstract: The homotrimeric human serine protease HtrA1 is homologous to bacterial HtrA proteases regarding the trypsin-like catalytic and PDZ domains but differs by the presence of an N-terminal domain with IGFBP and Kazal homology. The crystal structures and SAXS analysis presented herein reveal the rare tandem of IGFBP- and Kazal-like modules, a protease active site that adopts a competent conformation in the absence of substrate or inhibitor and a model for the intact protein in solution. Highly sensitive enzymatic assays and binding studies demonstrate that the N-terminal tandem has no apparent effect on protease activity, and in accordance with the structure-based predictions, neither the IGFBP- nor Kazal-like module retains the function of their prototype proteins. Our structures of the unliganded HtrA1 active site suggest two-state equilibrium and a "conformational selection" model, in which substrate binds to the active conformer.

PubMed: 22578544
DOI: 10.1016/j.str.2012.03.021

Experimental method

X-RAY DIFFRACTION (2.001 Å)