1gvl

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1gvl, resolution 1.80Å

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HUMAN PROKALLIKREIN 6 (HK6)/ PROZYME/ PROPROTEASE M/ PRONEUROSIN

Overview

Zyme/protease M/neurosin/human kallikrein 6 (hK6) is a member of the human, kallikrein family of trypsin-like serine proteinases and was originally, identified as being down-regulated in metastatic breast and ovarian tumors, when compared with corresponding primary tumors. Recent evidence suggests, that hK6 may serve as a circulating tumor marker in ovarian cancers. In, addition, it was described in the brain of Parkinson's disease and, Alzheimer's disease patients, where it is implicated in amyloid precursor, protein processing. It is thus a biomarker for these diseases. To examine, the mechanism of activation of hK6, we have solved the structure of its, proform, the first of a human kallikrein family member. The proenzyme, displays a fold that exhibits chimeric features between those of, trypsinogen and other family members. It lacks the characteristic, "kallikrein loop" and forms the six disulfide bridges of trypsin. Pro-hK6, displays a completely closed specificity pocket and a unique conformation, of the regions involved in structural rearrangements upon proteolytic, cleavage activation. This points to a novel activation mechanism, which, could be extrapolated to other human kallikreins.

About this Structure

1GVL is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The structure of human prokallikrein 6 reveals a novel activation mechanism for the kallikrein family., Gomis-Ruth FX, Bayes A, Sotiropoulou G, Pampalakis G, Tsetsenis T, Villegas V, Aviles FX, Coll M, J Biol Chem. 2002 Jul 26;277(30):27273-81. Epub 2002 May 16. PMID:12016211

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