Structural highlights
2wyk is a 1 chain structure with sequence from "bacterium_influenzae"_lehmann_and_neumann_1896 "bacterium influenzae" lehmann and neumann 1896. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , |
| Related: | 2xa5, 2cey, 2xwo, 2xwv, 2xwi, 2cex, 2wyp, 2v4c, 2xxk, 2xwk, 2wx9 |
| 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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Darby JF, Hopkins AP, Shimizu S, Roberts SM, Brannigan JA, Turkenburg JP, Thomas GH, Hubbard RE, Fischer M. Water Networks Can Determine the Affinity of Ligand Binding to Proteins. J Am Chem Soc. 2019 Oct 9;141(40):15818-15826. doi: 10.1021/jacs.9b06275. Epub, 2019 Sep 26. PMID:31518131 doi:http://dx.doi.org/10.1021/jacs.9b06275
