2V4C

Structure of sialic acid binding protein (SiaP) in the presence of KDN

Summary for 2V4C

• Entry DOI: 10.2210/pdb2v4c/pdb
• Related: 2CEX 2CEY 2WX9 2WYK 2WYP
• Descriptor: SIALIC ACID-BINDING PERIPLASMIC PROTEIN SIAP, deamino-beta-neuraminic acid (3 entities in total)
• Functional Keywords: transport protein, sugar transport, transport protein esr, trap
• Biological source: HAEMOPHILUS INFLUENZAE
• Total number of polymer chains: 1
• Total formula weight: 34886.40

Authors

Fischer, M.,Hubbard, R.E. (deposition date: 2008-09-18, release date: 2010-03-31, Last modification date: 2023-12-13)

Primary citation

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., 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

Experimental method

X-RAY DIFFRACTION (1.7 Å)