6dqq: Difference between revisions

<StructureSection load='6dqq' size='340' side='right' caption='[[6dqq]], [[Resolution|resolution]] 1.85&Aring;' scene=''>

<table><tr><td colspan='2'>[[6dqq]] 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=6DQQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DQQ FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6dqq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dqq OCA], [http://pdbe.org/6dqq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dqq RCSB], [http://www.ebi.ac.uk/pdbsum/6dqq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dqq ProSAT]</span></td></tr>

== Publication Abstract from PubMed ==

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.

 

== References ==

[[Category: Haei8]]

[[Category: Pinkett, H W]]

[[Category: Tanaka, K J]]

[[Category: Abc transporter]]

[[Category: Peptide binding protein]]

[[Category: Substrate-binding protein]]