1cjl

From Proteopedia

Revision as of 14:16, 12 November 2007

CRYSTAL STRUCTURE OF A CYSTEINE PROTEASE PROFORM

Overview

Cathepsin L is a member of the papain superfamily of cysteine proteases, and, like many other proteases, it is synthesized as an inactive, proenzyme. Its prosegment shows little homology to that of procathepsin B, whose structure, the first for a cysteine protease proenzyme, has been, determined recently. We report here the 3-D structure of a mutant of human, procathepsin L determined at 2.2 A resolution, describe the mode of, binding employed by the prosegment and discuss the molecular basis for, other possible roles of the prosegment. The N-terminal part of the, prosegment is globular and contains three alpha-helices with a small, hydrophobic core built around aromatic side chains. This domain packs, against a loop on the enzyme's surface, with the aromatic side chain from, the prosegment being located in the center of this loop and providing a, large contact area. The C-terminal portion of the prosegment assumes an, extended conformation and follows along the substrate binding cleft toward, the N-terminus of the mature enzyme. The direction of the prosegment in, the substrate binding cleft is opposite to that of substrates. The, previously described role of the prosegment in the interactions with, membranes is supported by the structure of its N-terminal domain. The fold, of the prosegment and the mechanism by which it inhibits the enzymatic, activity of procathepsin L is similar to that observed in procathepsin B, despite differences in length and sequence, suggesting that this mode of, inhibition is common to all enzymes from the papain superfamily.

About this Structure

1CJL is a Single protein structure of sequence from Homo sapiens. Active as Cathepsin L, with EC number 3.4.22.15 Structure known Active Site: ACT. Full crystallographic information is available from OCA.

Reference

Structure of human procathepsin L reveals the molecular basis of inhibition by the prosegment., Coulombe R, Grochulski P, Sivaraman J, Menard R, Mort JS, Cygler M, EMBO J. 1996 Oct 15;15(20):5492-503. PMID:8896443

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