2f21
From Proteopedia
|
human Pin1 Fip 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
2F21 is a Single protein structure of sequence from Homo sapiens with 1PE as ligand. 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
Page seeded by OCA on Mon Nov 12 21:58:36 2007
