6SVH

Protein allostery of the WW domain at atomic resolution: FFpSPR bound structure

Summary for 6SVH

• Entry DOI: 10.2210/pdb6svh/pdb
• Related: 6SVC 6SVE
• NMR Information: BMRB: 34434
• Descriptor: Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (1 entity in total)
• Functional Keywords: structure from cyana 3.98.12, peptide binding protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 4105.58

Authors

Strotz, D.,Orts, J.,Friedmann, M.,Guntert, P.,Vogeli, B.,Riek, R. (deposition date: 2019-09-18, release date: 2020-09-30, Last modification date: 2024-06-19)

Primary citation

Strotz, D.,Orts, J.,Kadavath, H.,Friedmann, M.,Ghosh, D.,Olsson, S.,Chi, C.N.,Pokharna, A.,Guntert, P.,Vogeli, B.,Riek, R.
Protein Allostery at Atomic Resolution.
Angew.Chem.Int.Ed.Engl., 59:22132-22139, 2020

PubMed Abstract: Protein allostery is a phenomenon involving the long range coupling between two distal sites in a protein. In order to elucidate allostery at atomic resoluion on the ligand-binding WW domain of the enzyme Pin1, multistate structures were calculated from exact nuclear Overhauser effect (eNOE). In its free form, the protein undergoes a microsecond exchange between two states, one of which is predisposed to interact with its parent catalytic domain. In presence of the positive allosteric ligand, the equilibrium between the two states is shifted towards domain-domain interaction, suggesting a population shift model. In contrast, the allostery-suppressing ligand decouples the side-chain arrangement at the inter-domain interface thereby reducing the inter-domain interaction. As such, this mechanism is an example of dynamic allostery. The presented distinct modes of action highlight the power of the interplay between dynamics and function in the biological activity of proteins.

PubMed: 32797659
DOI: 10.1002/anie.202008734

Experimental method

SOLUTION NMR