3iqi: Difference between revisions
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== | ==Structure of O-Acetylserine Sulfhydrylase in Complex with Peptide MNENI== | ||
[[3iqi]] is a 2 chain structure with sequence from [ | <StructureSection load='3iqi' size='340' side='right'caption='[[3iqi]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3iqi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Haemophilus_influenzae Haemophilus influenzae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IQI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3IQI FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LLP:(2S)-2-AMINO-6-[[3-HYDROXY-2-METHYL-5-(PHOSPHONOOXYMETHYL)PYRIDIN-4-YL]METHYLIDENEAMINO]HEXANOIC+ACID'>LLP</scene></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=3iqi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3iqi OCA], [https://pdbe.org/3iqi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3iqi RCSB], [https://www.ebi.ac.uk/pdbsum/3iqi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3iqi ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CYSK_HAEIN CYSK_HAEIN] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/iq/3iqi_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3iqi ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The inhibition of cysteine biosynthesis in prokaryotes and protozoa has been proposed to be relevant for the development of antibiotics. Haemophilus influenzae O-acetylserine sulfhydrylase (OASS), catalyzing l-cysteine formation, is inhibited by the insertion of the C-terminal pentapeptide (MNLNI) of serine acetyltransferase into the active site. Four-hundred MNXXI pentapeptides were generated in silico, docked into OASS active site using GOLD, and scored with HINT. The terminal P5 Ile accounts for about 50% of the binding energy. Glu or Asp at position P4 and, to a lesser extent, at position P3 also significantly contribute to the binding interaction. The predicted affinity of 14 selected pentapeptides correlated well with the experimentally determined dissociation constants. The X-ray structure of three high affinity pentapeptide-OASS complexes were compared with the docked poses. These results, combined with a GRID analysis of the active site, allowed us to define a pharmacophoric scaffold for the design of peptidomimetic inhibitors. | |||
Design of O-acetylserine sulfhydrylase inhibitors by mimicking nature.,Salsi E, Bayden AS, Spyrakis F, Amadasi A, Campanini B, Bettati S, Dodatko T, Cozzini P, Kellogg GE, Cook PF, Roderick SL, Mozzarelli A J Med Chem. 2010 Jan 14;53(1):345-56. PMID:19928859<ref>PMID:19928859</ref> | |||
<ref | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3iqi" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Haemophilus influenzae]] | [[Category: Haemophilus influenzae]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Roderick SL]] | ||
Latest revision as of 10:56, 6 September 2023
Structure of O-Acetylserine Sulfhydrylase in Complex with Peptide MNENIStructure of O-Acetylserine Sulfhydrylase in Complex with Peptide MNENI
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe inhibition of cysteine biosynthesis in prokaryotes and protozoa has been proposed to be relevant for the development of antibiotics. Haemophilus influenzae O-acetylserine sulfhydrylase (OASS), catalyzing l-cysteine formation, is inhibited by the insertion of the C-terminal pentapeptide (MNLNI) of serine acetyltransferase into the active site. Four-hundred MNXXI pentapeptides were generated in silico, docked into OASS active site using GOLD, and scored with HINT. The terminal P5 Ile accounts for about 50% of the binding energy. Glu or Asp at position P4 and, to a lesser extent, at position P3 also significantly contribute to the binding interaction. The predicted affinity of 14 selected pentapeptides correlated well with the experimentally determined dissociation constants. The X-ray structure of three high affinity pentapeptide-OASS complexes were compared with the docked poses. These results, combined with a GRID analysis of the active site, allowed us to define a pharmacophoric scaffold for the design of peptidomimetic inhibitors. Design of O-acetylserine sulfhydrylase inhibitors by mimicking nature.,Salsi E, Bayden AS, Spyrakis F, Amadasi A, Campanini B, Bettati S, Dodatko T, Cozzini P, Kellogg GE, Cook PF, Roderick SL, Mozzarelli A J Med Chem. 2010 Jan 14;53(1):345-56. PMID:19928859[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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