1zcn

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spinqualitylabelsall models 1zcn, resolution 1.9Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

human Pin1 Ng mutant

Overview

Protein folding barriers result from a combination of factors including, unavoidable energetic frustration from nonnative interactions, natural, variation and selection of the amino acid sequence for function, and/or, selection pressure against aggregation. The rate-limiting step for human, Pin1 WW domain folding is the formation of the loop 1 substructure. The, native conformation of this six-residue loop positions side chains that, are important for mediating protein-protein interactions through the, binding of Pro-rich sequences. Replacement of the wild-type loop 1 primary, structure by shorter sequences with a high propensity to fold into a, type-I' beta-turn conformation or the statistically preferred type-I G1, bulge conformation accelerates WW domain folding by almost an order of, magnitude and increases thermodynamic stability. However, loop engineering, to optimize folding energetics has a significant downside: it effectively, eliminates WW domain function according to ligand-binding studies. The, energetic contribution of loop 1 to ligand binding appears to have evolved, at the expense of fast folding and additional protein stability. Thus, the, two-state barrier exhibited by the wild-type human Pin1 WW domain, principally results from functional requirements, rather than from, physical constraints inherent to even the most efficient loop formation, process.

About this Structure

1ZCN is a Single protein structure of sequence from Homo sapiens with PO4 and 1PE as ligands. Active as Peptidylprolyl isomerase, with EC number 5.2.1.8 Full crystallographic information is available from OCA.

Reference

Structure-function-folding relationship in a WW domain., Jager M, Zhang Y, Bieschke J, Nguyen H, Dendle M, Bowman ME, Noel JP, Gruebele M, Kelly JW, Proc Natl Acad Sci U S A. 2006 Jul 11;103(28):10648-53. Epub 2006 Jun 28. PMID:16807295

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