PDBsum entry 2kbu

Isomerase

PDB id: 2kbu

Contents

Protein chain

31 a.a. *

* Residue conservation analysis

PDB id:

2kbu

Name:

Isomerase

Title:

Nmr solution structure of pin1 ww domain mutant with beta turn mimic at position 12

Structure:

Peptidyl-prolyl cis-trans isomerase nima-interacting 1. Chain: a. Fragment: unp residues 6-39. Synonym: rotamase pin1, ppiase pin1. Engineered: yes. Mutation: yes. Other_details: residues rssg replaced by the beta-turn mimic cfd

Source:

Synthetic: yes. Other_details: residues rssg replaced by the beta-turn mimic cfd

NMR struc:

15 models

Authors:

A.A.Fuller,G.Bhabha,D.A.Case

Key ref:

A.A.Fuller et al. (2009). Evaluating beta-turn mimics as beta-sheet folding nucleators. Proc Natl Acad Sci U S A, 106, 11067-11072. PubMed id: 19541614 DOI: 10.1073/pnas.0813012106

Date:

08-Dec-08 Release date: 07-Jul-09

Protein chain

Q13526  (PIN1_HUMAN) -  Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 from Homo sapiens

Seq: 163 a.a.

Struc: 31 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.5.2.1.8 - peptidylprolyl isomerase.
• Reaction: [protein]-peptidylproline (omega=180) = [protein]-peptidylproline (omega=0)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1073/pnas.0813012106

Proc Natl Acad Sci U S A 106:11067-11072 (2009)

PubMed id: 19541614

Evaluating beta-turn mimics as beta-sheet folding nucleators.

A.A.Fuller, D.Du, F.Liu, J.E.Davoren, G.Bhabha, G.Kroon, D.A.Case, H.J.Dyson, E.T.Powers, P.Wipf, M.Gruebele, J.W.Kelly.

ABSTRACT

Beta-turns are common conformations that enable proteins to adopt globular structures, and their formation is often rate limiting for folding. Beta-turn mimics, molecules that replace the i + 1 and i + 2 amino acid residues of a beta-turn, are envisioned to act as folding nucleators by preorganizing the pendant polypeptide chains, thereby lowering the activation barrier for beta-sheet formation. However, the crucial kinetic experiments to demonstrate that beta-turn mimics can act as strong nucleators in the context of a cooperatively folding protein have not been reported. We have incorporated 6 beta-turn mimics simulating varied beta-turn types in place of 2 residues in an engineered beta-turn 1 or beta-bulge turn 1 of the Pin 1 WW domain, a three-stranded beta-sheet protein. We present 2 lines of kinetic evidence that the inclusion of beta-turn mimics alters beta-sheet folding rates, enabling us to classify beta-turn mimics into 3 categories: those that are weak nucleators but permit Pin WW folding, native-like nucleators, and strong nucleators. Strong nucleators accelerate folding relative to WW domains incorporating all alpha-amino acid sequences. A solution NMR structure reveals that the native Pin WW beta-sheet structure is retained upon incorporating a strong E-olefin nucleator. These beta-turn mimics can now be used to interrogate protein folding transition state structures and the 2 kinetic analyses presented can be used to assess the nucleation capacity of other beta-turn mimics.

Selected figure(s)

Figure 1.
β-Turn mimics studied.

Figure 2.
Comparison of the solution structures of the Pin1 WW domain. (A) Superposition of 12 structures of the WT protein (36; PDB ID code 2kcf) (B) Superposition of 15 structures of variant C-4 (PDB ID code 2kbu). (C) Superposition of a low-energy structure from each of the ensembles in (A) and (B). The inset shows the structure of dipeptide replacement 4 in loop 1.

Figures were selected by an automated process.