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1zcn
From Proteopedia
| |||||||
| , resolution 1.9Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | PIN1 (Homo sapiens) | ||||||
| Activity: | Peptidylprolyl isomerase, with EC number 5.2.1.8 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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 Thu Mar 20 15:33:51 2008
Categories: Homo sapiens | Peptidylprolyl isomerase | Single protein | Bowman, M E. | Dendel, G. | Gruebele, M. | Jager, M. | Kelly, J W. | Nguyen, H. | Noel, J P. | Zhang, Y. | 1PE | PO4 | Type i beta-turn | Ww domain
