3b50
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(New page: 200px<br /><applet load="3b50" size="350" color="white" frame="true" align="right" spinBox="true" caption="3b50, resolution 1.400Å" /> '''Structure of H. inf...)
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Revision as of 08:47, 23 January 2008
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Structure of H. influenzae sialic acid binding protein bound to Neu5Ac.
Overview
Nontypeable Haemophilus influenzae is an opportunistic human pathogen, causing otitis media in children and chronic bronchitis and pneumonia in, patients with chronic obstructive pulmonary disease. The outer membrane of, nontypeable H. influenzae is dominated by lipooligosaccharides (LOS), many, of which incorporate sialic acid as a terminal non-reducing sugar. Sialic, acid has been demonstrated to be an important factor in the survival of, the bacteria within the host environment. H. influenzae is incapable of, synthesizing sialic acid and is dependent on scavenging free sialic acid, from the host environment. To achieve this, H. influenzae utilizes a, tripartite ATP-independent periplasmic transporter. In this paper, we, characterize the binding site of the extracytoplasmic solute receptor, (SiaP) from nontypeable H. influenzae strain 2019. A crystal structure of, Neu5Ac-bound SiaP was determined to 1.4 A resolution. Thermodynamic, characterization of Neu5Ac binding shows this interaction is enthalpically, driven with a substantial unfavorable contribution from entropy. This is, expected because the binding of SiaP to Neu5AC is mediated by numerous, hydrogen bonds and has several buried water molecules. Point mutations, targeting specific amino acids were introduced in the putative binding, site. Complementation with the mutated siaP constructs resulted either in, full, partial, or no complementation, depending on the role of specific, residues. Mass spectrometry analysis of the O-deacylated LOS of the R127K, point mutation confirmed the observation of reduced incorporation of, Neu5Ac into the LOS. The decreased ability of H. influenzae to import, sialic acid had negative effects on resistance to complement-mediated, killing and viability of biofilms in vitro, confirming the importance of, sialic acid transport to the bacterium.
About this Structure
3B50 is a Single protein structure of sequence from Haemophilus influenzae with as ligand. Full crystallographic information is available from OCA.
Reference
Characterization of the N-acetyl-5-neuraminic acid binding site of the extracytoplasmic solute receptor (SiaP) of nontypeable Haemophilus influenzae strain 2019., Johnston JW, Coussens NP, Allen S, Houtman JC, Turner KH, Zaleski A, Ramaswamy S, Gibson BW, Apicella MA, J Biol Chem. 2007 Oct 18;. PMID:17947229
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