PDBsum entry 2v4c

Transport protein

PDB id: 2v4c

Contents

Protein chain

309 a.a. *

Ligands

KDN

Waters ×346

* Residue conservation analysis

PDB id:

2v4c

Name:

Transport protein

Title:

Structure of sialic acid binding protein (siap) in the presence of kdn

Structure:

Sialic acid-binding periplasmic protein siap. Chain: a. Synonym: sialic acid binding protein, n-acetylneuraminic -binding protein, neu5ac-binding protein, extracytoplasmic solute receptor protein siap. Engineered: yes

Source:

Haemophilus influenzae. Organism_taxid: 727. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.70Å R-factor: 0.146 R-free: 0.194

Authors:

M.Fischer,R.E.Hubbard

Key ref:

J.F.Darby et al. (2019). Water Networks Can Determine the Affinity of Ligand Binding to Proteins. J Am Chem Soc, 141, 15818-15826. PubMed id: 31518131 DOI: 10.1021/jacs.9b06275

Date:

18-Sep-08 Release date: 31-Mar-10

Protein chain

P44542  (SIAP_HAEIN) -  Sialic acid-binding periplasmic protein SiaP from Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)

Seq: 329 a.a.

Struc: 309 a.a.

DOI no: 10.1021/jacs.9b06275

J Am Chem Soc 141:15818-15826 (2019)

PubMed id: 31518131

Water Networks Can Determine the Affinity of Ligand Binding to Proteins.

J.F.Darby, A.P.Hopkins, S.Shimizu, S.M.Roberts, J.A.Brannigan, J.P.Turkenburg, G.H.Thomas, R.E.Hubbard, M.Fischer.

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 Haemophilus influenzae 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.