Crystal structure of human cathepsin S

75Citations
Citations of this article
31Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

We have determined the 2.5 Å, structure (R(cryst) = 20.5%, R(free) = 28.5%) of a complex between human cathepsin S and the potent, irreversible inhibitor 4-morpholinecarbonyl-Phe-hPhe-vinyl sulfone-phenyl. Noncrystallographic symmetry averaging and other density modification techniques were used to improve electron density maps which were nonoptimal due to systematically incomplete data. Methods that reduce the number of parameters were implemented for refinement. The refined structure shows cathepsin S to be similar to related cysteine proteases such as papain and cathepsins K and L. As expected, the covalently-bound inhibitor is attached to the enzyme at Cys 25, and enzyme binding subsites S3-S1' are occupied by the respective inhibitor substituents. A somewhat larger S2 pocket than what is found in similar enzymes is consistent with the broader specificity of cathepsin S at this site, while Lys 61 in the S3 site may offer opportunities for selective inhibition of this enzyme. The presence of Arg 137 in the S1' pocket, and proximal to Cys 25 may have implications not only for substrate specificity C-terminal to the scissile bond, but also for catalysis.

Cite

CITATION STYLE

APA

McGrath, M. E., Palmer, J. T., Brömme, D., & Somoza, J. R. (1998). Crystal structure of human cathepsin S. Protein Science, 7(6), 1294–1302. https://doi.org/10.1002/pro.5560070604

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free