View source for 2woq


==Porphobilinogen Synthase (HemB) in Complex with 5-acetamido-4- oxohexanoic acid (Alaremycin 2)==
<StructureSection load='2woq' size='340' side='right'caption='[[2woq]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2woq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WOQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WOQ 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]] 1.75&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AYC:ALAREMYCIN+2'>AYC</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PE5:3,6,9,12,15,18,21,24-OCTAOXAHEXACOSAN-1-OL'>PE5</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=2woq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2woq OCA], [https://pdbe.org/2woq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2woq RCSB], [https://www.ebi.ac.uk/pdbsum/2woq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2woq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HEM2_PSEAE HEM2_PSEAE] Catalyzes an early step in the biosynthesis of tetrapyrroles. Binds two molecules of 5-aminolevulinate per subunit, each at a distinct site, and catalyzes their condensation to form porphobilinogen (By similarity).
== 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/wo/2woq_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2woq ConSurf].
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== Publication Abstract from PubMed ==
The recently discovered antibacterial compound alaremycin, produced by Streptomyces sp. A012304, structurally closely resembles 5-aminolevulinic acid, the substrate of porphobilinogen synthase. During the initial steps of heme biosynthesis, two molecules of 5-aminolevulinic acid are asymmetrically condensed to porphobilinogen. Alaremycin was found to efficiently inhibit the growth of both Gram-negative and Gram-positive bacteria. Using the newly created heme-permeable strain Escherichia coli CSA1, we are able to uncouple heme biosynthesis from bacterial growth and demonstrate that alaremycin targets the heme biosynthetic pathway. Further studies focused on the activity of alaremycin against the opportunistic pathogenic bacterium Pseudomonas aeruginosa. The MIC of alaremycin was determined to be 12 mM. Alaremycin was identified as a direct inhibitor of recombinant purified P. aeruginosa porphobilinogen synthase and had a K(i) of 1.33 mM. To understand the molecular basis of alaremycin's antibiotic activity at the atomic level, the P. aeruginosa porphobilinogen synthase was cocrystallized with the alaremycin. At 1.75-A resolution, the crystal structure reveals that the antibiotic efficiently blocks the active site of porphobilinogen synthase. The antibiotic binds as a reduced derivative of 5-acetamido-4-oxo-5-hexenoic acid. The corresponding methyl group is, however, not coordinated by any amino acid residues of the active site, excluding its functional relevance for alaremycin inhibition. Alaremycin is covalently bound by the catalytically important active-site lysine residue 260 and is tightly coordinated by several active-site amino acids. Our data provide a solid structural basis to further improve the activity of alaremycin for rational drug design. Potential approaches are discussed.

Structure of the heme biosynthetic Pseudomonas aeruginosa porphobilinogen synthase in complex with the antibiotic alaremycin.,Heinemann IU, Schulz C, Schubert WD, Heinz DW, Wang YG, Kobayashi Y, Awa Y, Wachi M, Jahn D, Jahn M Antimicrob Agents Chemother. 2010 Jan;54(1):267-72. Epub 2009 Oct 12. PMID:19822707<ref>PMID:19822707</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Porphobilinogen synthase|Porphobilinogen synthase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Pseudomonas aeruginosa]]
[[Category: Awa Y]]
[[Category: Heinemann IU]]
[[Category: Heinz DW]]
[[Category: Jahn D]]
[[Category: Jahn M]]
[[Category: Kobayashi Y]]
[[Category: Schubert W-D]]
[[Category: Schulz C]]
[[Category: Wachi M]]
[[Category: Wang Y-G]]