1iz2

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Revision as of 15:29, 12 November 2007

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spinqualitylabelsall models 1iz2, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Interactions causing the kinetic trap in serpin protein folding

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

Conformational transition is fundamental to the mechanism of functional, regulation in proteins, and serpins (serine protease inhibitors) can, provide insight into this process. Serpins are metastable in their native, forms, and they ordinarily undergo conformational transition to a stable, state only when they form a tight complex with target proteases. The, metastable native form is thus considered to be a kinetically trapped, folding intermediate. We sought to understand the nature of the serpin, kinetic trap as a step toward discovering how conformational transition is, regulated. We found that mutations of the B/C beta-barrel of native, alpha(1)-antitrypsin, a prototypical serpin, allowed conversion of the, molecule into a more stable state. A 2.2 A resolution crystal structure of, the stable form (PDB code, ) showed that the reactive site loop is, inserted into an A beta-sheet, as in the latent plasminogen activator, inhibitor-1. Mutational analyses suggest strongly that interactions not, found in the final stable form cause the kinetic trap in serpin protein, folding.

Disease

Known diseases associated with this structure: Emphysema OMIM:[107400], Emphysema-cirrhosis OMIM:[107400], Hemorrhagic diathesis due to antithrombin Pittsburgh OMIM:[107400], Pulmonary disease, chronic obstructive, susceptibility to OMIM:[107400]

About this Structure

1IZ2 is a Single protein structure of sequence from Homo sapiens with SUM as ligand. Full crystallographic information is available from OCA.

Reference

Interactions causing the kinetic trap in serpin protein folding., Im H, Woo MS, Hwang KY, Yu MH, J Biol Chem. 2002 Nov 29;277(48):46347-54. Epub 2002 Sep 18. PMID:12244055

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