1deu
From Proteopedia
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CRYSTAL STRUCTURE OF HUMAN PROCATHEPSIN X: A CYSTEINE PROTEASE WITH THE PROREGION COVALENTLY LINKED TO THE ACTIVE SITE CYSTEINE
Overview
Human cathepsin X is one of many proteins discovered in recent years, through the mining of sequence databases. Its sequence shows clear, homology to cysteine proteases from the papain family, containing the, characteristic residue patterns, including the active site. However, the, proregion of cathepsin X is only 38 residues long, the shortest among, papain-like enzymes, and the cathepsin X sequence has an atypical, insertion in the regions proximal to the active site. This protein was, recently expressed and partially characterized biochemically. Unlike most, other cysteine proteases from the papain family, procathepsin X is, incapable of autoprocessing in vitro but can be processed under reducing, conditions by exogenous cathepsin L. Atypically, the mature enzyme is, primarily a carboxypeptidase and has extremely poor endopeptidase, activity. We have determined the three-dimensional structure of the, procathepsin X at 1.7 A resolution. The overall structure of the mature, enzyme is characteristic for enzymes of the papain superfamily, but, contains several novel features. Most interestingly, the short proregion, binds to the enzyme with the aid of a covalent bond between the cysteine, residue in the proregion (Cys10p) and the active site cysteine residue, (Cys31). This is the first example of a zymogen in which the inhibition of, enzyme's proteolytic activity by the proregion is achieved through a, reversible covalent modification of the active site nucleophile. Such mode, of binding requires less contact area between the proregion and the enzyme, than observed in other procathepsins, and no auxiliary binding site on the, enzyme surface is used. A three-residue insertion in a highly conserved, region, just prior to the active site cysteine residue, confers a, significantly different shape on the S' subsites, compared to other, proteases from papain family. The 3D structure provides an explanation for, the rather unusual carboxypeptidase activity of this enzyme and confirms, the predictions based on homology modeling. Another long insertion in the, cathepsin X amino acid sequence forms a beta-hairpin pointing away from, the active site. This insertion, thought to be an equivalent of cathepsin, B occluding loop, is located on the side of the protein, distant from the, substrate binding site.
About this Structure
1DEU is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of human procathepsin X: a cysteine protease with the proregion covalently linked to the active site cysteine., Sivaraman J, Nagler DK, Zhang R, Menard R, Cygler M, J Mol Biol. 2000 Jan 28;295(4):939-51. PMID:10656802
Page seeded by OCA on Mon Nov 12 16:31:38 2007
