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| | ==Structure of H. influenzae sialic acid binding protein bound to Neu5Ac.== | | ==Structure of H. influenzae sialic acid binding protein bound to Neu5Ac.== |
| - | <StructureSection load='3b50' size='340' side='right' caption='[[3b50]], [[Resolution|resolution]] 1.40Å' scene=''> | + | <StructureSection load='3b50' size='340' side='right'caption='[[3b50]], [[Resolution|resolution]] 1.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3b50]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacterium_influenzae"_lehmann_and_neumann_1896 "bacterium influenzae" lehmann and neumann 1896]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3B50 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3B50 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3b50]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacterium_influenzae"_lehmann_and_neumann_1896 "bacterium influenzae" lehmann and neumann 1896]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3B50 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3B50 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SLB:5-N-ACETYL-BETA-D-NEURAMINIC+ACID'>SLB</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SLB:5-N-ACETYL-BETA-D-NEURAMINIC+ACID'>SLB</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2cex|2cex]], [[2cey|2cey]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2cex|2cex]], [[2cey|2cey]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">siaP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=727 "Bacterium influenzae" Lehmann and Neumann 1896])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">siaP ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=727 "Bacterium influenzae" Lehmann and Neumann 1896])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3b50 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3b50 OCA], [http://pdbe.org/3b50 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3b50 RCSB], [http://www.ebi.ac.uk/pdbsum/3b50 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3b50 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3b50 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3b50 OCA], [https://pdbe.org/3b50 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3b50 RCSB], [https://www.ebi.ac.uk/pdbsum/3b50 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3b50 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SIAP_HAEIN 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. | + | [[https://www.uniprot.org/uniprot/SIAP_HAEIN 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. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Bacterium influenzae lehmann and neumann 1896]] | | [[Category: Bacterium influenzae lehmann and neumann 1896]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Apicella, M A]] | | [[Category: Apicella, M A]] |
| | [[Category: Coussens, N P]] | | [[Category: Coussens, N P]] |
| Structural highlights
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.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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 nonreducing 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 study, we characterize the binding site of the extracytoplasmic solute receptor (SiaP) from nontypeable H. influenzae strain 2019. A crystal structure of N-acetyl-5-neuraminic acid (Neu5Ac)-bound SiaP was determined to 1.4A 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.
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. 2008 Jan 11;283(2):855-65. Epub 2007 Oct 18. PMID:17947229[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Johnston JW, Coussens NP, Allen S, Houtman JC, Turner KH, Zaleski A, Ramaswamy S, Gibson BW, Apicella MA. Characterization of the N-acetyl-5-neuraminic acid-binding site of the extracytoplasmic solute receptor (SiaP) of nontypeable Haemophilus influenzae strain 2019. J Biol Chem. 2008 Jan 11;283(2):855-65. Epub 2007 Oct 18. PMID:17947229 doi:10.1074/jbc.M706603200
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