6H75

SiaP A11N in complex with Neu5Ac (RT)

6H75 の概要

• エントリーDOI: 10.2210/pdb6h75/pdb
• 分子名称: Sialic acid-binding periplasmic protein SiaP, N-acetyl-beta-neuraminic acid (3 entities in total)
• 機能のキーワード: trap transporter, sialic acid, transport protein
• 由来する生物種: Haemophilus influenzae Rd KW20
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35384.91

構造登録者

Fischer, M.,Darby, J.F.,Brannigan, J.A.,Turkenburg, J.,Hubbard, R.E. (登録日: 2018-07-30, 公開日: 2019-08-14, 最終更新日: 2024-05-15)

主引用文献

Darby, J.F.,Hopkins, A.P.,Shimizu, S.,Roberts, S.M.,Brannigan, J.A.,Turkenburg, J.P.,Thomas, G.H.,Hubbard, R.E.,Fischer, M.
Water Networks Can Determine the Affinity of Ligand Binding to Proteins.
J.Am.Chem.Soc., 141:15818-15826, 2019

PubMed Abstract: Solvent organization is a key but underexploited contributor to the thermodynamics of protein-ligand recognition, with implications for ligand discovery, drug resistance, and protein engineering. Here, we explore the contribution of solvent to ligand binding in the virulence protein SiaP. By introducing a single mutation without direct ligand contacts, we observed a >1000-fold change in sialic acid binding affinity. Crystallographic and calorimetric data of wild-type and mutant SiaP showed that this change results from an enthalpically unfavorable perturbation of the solvent network. This disruption is reflected by changes in the normalized atomic displacement parameters of crystallographic water molecules. In SiaP's enclosed cavity, relative differences in water-network dynamics serve as a simple predictor of changes in the free energy of binding upon changing protein, ligand, or both. This suggests that solvent structure is an evolutionary constraint on protein sequence that contributes to ligand affinity and selectivity.

PubMed: 31518131
DOI: 10.1021/jacs.9b06275

実験手法

X-RAY DIFFRACTION (1.45 Å)