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| ==Crystal structure of Haemophilus influenzae OppA complex with RPPGFSPFR== | | ==Crystal structure of Haemophilus influenzae OppA complex with RPPGFSPFR== |
| <StructureSection load='6dth' size='340' side='right' caption='[[6dth]], [[Resolution|resolution]] 1.96Å' scene=''> | | <StructureSection load='6dth' size='340' side='right'caption='[[6dth]], [[Resolution|resolution]] 1.96Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6dth]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Haei8 Haei8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DTH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DTH FirstGlance]. <br> | | <table><tr><td colspan='2'>[[6dth]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Haemophilus_influenzae_86-028NP Haemophilus influenzae 86-028NP]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DTH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DTH FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.96Å</td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6dqq|6dqq]], [[6dqr|6dqr]], [[6dqt|6dqt]], [[6dqu|6dqu]], [[6dtf|6dtf]], [[6dtg|6dtg]]</td></tr>
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">oppA, NTHI1292 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=281310 HAEI8])</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=6dth FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dth OCA], [https://pdbe.org/6dth PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dth RCSB], [https://www.ebi.ac.uk/pdbsum/6dth PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dth ProSAT]</span></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=6dth FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dth OCA], [http://pdbe.org/6dth PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dth RCSB], [http://www.ebi.ac.uk/pdbsum/6dth PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dth ProSAT]</span></td></tr> | |
| </table> | | </table> |
| <div style="background-color:#fffaf0;">
| | == Function == |
| == Publication Abstract from PubMed == | | [https://www.uniprot.org/uniprot/Q4QLH0_HAEI8 Q4QLH0_HAEI8] |
| In nontypeable Haemophilus influenzae (NTHi), the oligopeptide-binding protein OppA serves as the substrate-binding protein (SBP) responsible for peptide import. As a heme auxotroph, NTHi also uses host hemoproteins as an iron source. OppA is a member of the Cluster C SBP family, and unlike other SBP families, some members recognize two distinctly different substrates. DppA (dipeptide), MppA (murein tripeptide), and SapA (antimicrobial peptides) are Cluster C proteins known to also transport heme. However, the ability of OppA to participate in heme binding and how Cluster C proteins accommodate these heme and peptide substrates are unclear. Here, we solved the crystal structure of nthiOppA in complex with hydrophobic peptides of various sizes. The hexapeptide complex revealed the flexibility of nthiOppA's binding cavity to expand and accommodate a longer peptide substrate while maintaining similar protein-peptide interactions used to bind smaller peptides. Additionally, we observed the multifunctional heme binding of nthiOppA, and using surface plasmon resonance (SPR), we established heme specificity and affinity of the four Cluster C proteins in NTHi. Ligand-docking studies predicted a distinct heme-specific cleft in the nthiOppA substrate-binding pocket, and SPR competition assays confirmed that heme does not directly compete with peptides in this pocket. Additionally, we noted that the individual nthiOppA domains differentially contribute to substrate binding, with one domain playing a dominant role in heme binding and the other in peptide binding. Our results identified multi-substrate specificity of nthiOppA and distinguished the roles of NTHi Cluster C proteins in the heme-uptake pathway of this bacterial pathogen.
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| Oligopeptide-binding protein from nontypeable Haemophilus influenzae has ligand-specific sites to accommodate peptides and heme in the binding pocket.,Tanaka KJ, Pinkett HW J Biol Chem. 2018 Nov 19. pii: RA118.004479. doi: 10.1074/jbc.RA118.004479. PMID:30455346<ref>PMID:30455346</ref>
| | ==See Also== |
| | | *[[ABC transporter 3D structures|ABC transporter 3D structures]] |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 6dth" style="background-color:#fffaf0;"></div>
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| == References == | |
| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Haei8]] | | [[Category: Haemophilus influenzae 86-028NP]] |
| [[Category: Pinkett, H W]] | | [[Category: Large Structures]] |
| [[Category: Tanaka, K J]] | | [[Category: Pinkett HW]] |
| [[Category: Abc transporter]] | | [[Category: Tanaka KJ]] |
| [[Category: Peptide binding protein]]
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| [[Category: Substrate-binding protein]]
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