2wx9

Crystal structure of the sialic acid binding periplasmic protein SiaP

spinqualitylabelsall models 2wx9, resolution 1.37Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2wx9 is a 1 chain structure with sequence from Haemophilus influenzae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NGE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SIAP_HAEIN Part of the tripartite ATP-independent periplasmic (TRAP) transport system SiaPT involved in the uptake of sialic acid. This protein specifically binds sialic acid with high affinity. Publication Abstract from PubMed 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. Water Networks Can Determine the Affinity of Ligand Binding to Proteins.,Darby JF, Hopkins AP, Shimizu S, Roberts SM, Brannigan JA, Turkenburg JP, Thomas GH, Hubbard RE, Fischer M J Am Chem Soc. 2019 Oct 9;141(40):15818-15826. doi: 10.1021/jacs.9b06275. Epub, 2019 Sep 26. PMID:31518131 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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