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| | <StructureSection load='7a5c' size='340' side='right'caption='[[7a5c]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='7a5c' size='340' side='right'caption='[[7a5c]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7a5c]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Vibch Vibch]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7A5C OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7A5C FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7a5c]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Vibrio_cholerae_O1_biovar_El_Tor_str._N16961 Vibrio cholerae O1 biovar El Tor str. N16961]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7A5C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A5C FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=R1A:3-{[(2,2,5,5-TETRAMETHYL-1-OXO-2,5-DIHYDRO-1H-PYRROLIUM-3-YL)METHYL]DISULFANYL}-D-ALANINE'>R1A</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=R1A:3-{[(2,2,5,5-TETRAMETHYL-1-OXO-2,5-DIHYDRO-1H-PYRROLIUM-3-YL)METHYL]DISULFANYL}-D-ALANINE'>R1A</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">siaP, VC_1779 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=243277 VIBCH])</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=7a5c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a5c OCA], [https://pdbe.org/7a5c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a5c RCSB], [https://www.ebi.ac.uk/pdbsum/7a5c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a5c ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7a5c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a5c OCA], [http://pdbe.org/7a5c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7a5c RCSB], [http://www.ebi.ac.uk/pdbsum/7a5c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7a5c ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SIAP_VIBCH SIAP_VIBCH]] Part of the tripartite ATP-independent periplasmic (TRAP) transport system SiaPQM that catalyzes unidirectional Na(+)-dependent sialic acid uptake. Binds the common sialic acid N-acetylneuraminic acid (Neu5Ac) with a high affinity.<ref>PMID:22167185</ref> <ref>PMID:22556361</ref> | + | [https://www.uniprot.org/uniprot/SIAP_VIBCH SIAP_VIBCH] Part of the tripartite ATP-independent periplasmic (TRAP) transport system SiaPQM that catalyzes unidirectional Na(+)-dependent sialic acid uptake. Binds the common sialic acid N-acetylneuraminic acid (Neu5Ac) with a high affinity.<ref>PMID:22167185</ref> <ref>PMID:22556361</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Vibch]] | + | [[Category: Vibrio cholerae O1 biovar El Tor str. N16961]] |
| - | [[Category: Glaenzer, J]] | + | [[Category: Glaenzer J]] |
| - | [[Category: Hagelueken, G]] | + | [[Category: Hagelueken G]] |
| - | [[Category: Peter, M F]] | + | [[Category: Peter MF]] |
| - | [[Category: Substrate binding protein]]
| + | |
| - | [[Category: Transport protein]]
| + | |
| - | [[Category: Transporter]]
| + | |
| - | [[Category: Trap]]
| + | |
| Structural highlights
Function
SIAP_VIBCH Part of the tripartite ATP-independent periplasmic (TRAP) transport system SiaPQM that catalyzes unidirectional Na(+)-dependent sialic acid uptake. Binds the common sialic acid N-acetylneuraminic acid (Neu5Ac) with a high affinity.[1] [2]
Publication Abstract from PubMed
The pathogens Vibrio cholerae and Haemophilus influenzae use tripartite ATP-independent periplasmic transporters (TRAPs) to scavenge sialic acid from host tissues. They use it as a nutrient or to evade the innate immune system by sialylating surface lipopolysaccharides. An essential component of TRAP transporters is a periplasmic substrate binding protein (SBP). Without substrate, the SBP has been proposed to rest in an open-state, which is not recognised by the transporter. Substrate binding induces a conformational change of the SBP and it is thought that this closed state is recognised by the transporter, triggering substrate translocation. Here we use real time single molecule FRET experiments and crystallography to investigate the open- to closed-state transition of VcSiaP, the SBP of the sialic acid TRAP transporter from V. cholerae. We show that the conformational switching of VcSiaP is strictly substrate induced, confirming an important aspect of the proposed transport mechanism. Two new crystal structures of VcSiaP provide insights into the closing mechanism. While the first structure contains the natural ligand, sialic acid, the second structure contains an artificial peptide in the sialic acid binding site. Together, the two structures suggest that the ligand itself stabilises the closed state and that SBP closure is triggered by physically bridging the gap between the two lobes of the SBP. Finally, we demonstrate that the affinity for the artificial peptide substrate can be substantially increased by varying its amino acid sequence and by this, serve as a starting point for the development of peptide-based inhibitors of TRAP transporters.
Triggering closure of a sialic acid TRAP transporter substrate binding protein through binding of natural or artificial substrates.,Peter MF, Gebhardt C, Glaenzer J, Schneberger N, de Boer M, Thomas GH, Cordes T, Hagelueken G J Mol Biol. 2020 Dec 11:166756. doi: 10.1016/j.jmb.2020.166756. PMID:33316271[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Mulligan C, Leech AP, Kelly DJ, Thomas GH. The membrane proteins SiaQ and SiaM form an essential stoichiometric complex in the sialic acid tripartite ATP-independent periplasmic (TRAP) transporter SiaPQM (VC1777-1779) from Vibrio cholerae. J Biol Chem. 2012 Jan 27;287(5):3598-608. doi: 10.1074/jbc.M111.281030. Epub 2011, Dec 13. PMID:22167185 doi:http://dx.doi.org/10.1074/jbc.M111.281030
- ↑ Chowdhury N, Norris J, McAlister E, Lau SYK, Thomas GH, Boyd EF. The VC1777-VC1779 proteins are members of a sialic acid-specific subfamily of TRAP transporters (SiaPQM) and constitute the sole route of sialic acid uptake in the human pathogen Vibrio cholerae. Microbiology (Reading). 2012 Aug;158(Pt 8):2158-2167. doi:, 10.1099/mic.0.059659-0. Epub 2012 May 3. PMID:22556361 doi:http://dx.doi.org/10.1099/mic.0.059659-0
- ↑ Peter MF, Gebhardt C, Glaenzer J, Schneberger N, de Boer M, Thomas GH, Cordes T, Hagelueken G. Triggering closure of a sialic acid TRAP transporter substrate binding protein through binding of natural or artificial substrates. J Mol Biol. 2020 Dec 11:166756. doi: 10.1016/j.jmb.2020.166756. PMID:33316271 doi:http://dx.doi.org/10.1016/j.jmb.2020.166756
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