View source for 3daq


==Crystal structure of dihydrodipicolinate synthase from methicillin-resistant Staphylococcus aureus==
<StructureSection load='3daq' size='340' side='right'caption='[[3daq]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3daq]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_MRSA252 Staphylococcus aureus subsp. aureus MRSA252]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DAQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DAQ 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]] 1.45&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=3daq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3daq OCA], [https://pdbe.org/3daq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3daq RCSB], [https://www.ebi.ac.uk/pdbsum/3daq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3daq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DAPA_STAAR DAPA_STAAR] Catalyzes the condensation of (S)-aspartate-beta-semialdehyde [(S)-ASA] and pyruvate to 4-hydroxy-tetrahydrodipicolinate (HTPA).<ref>PMID:18684709</ref> 
== 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/da/3daq_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=3daq ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Dihydrodipicolinate synthase (DHDPS) catalyzes the first committed step of the lysine biosynthetic pathway. The tetrameric structure of DHDPS is thought to be essential for enzymatic activity, as isolated dimeric mutants of Escherichia coli DHDPS possess less than 2.5% that of the activity of the wild-type tetramer. It has recently been proposed that the dimeric form lacks activity due to increased dynamics. Tetramerization, by buttressing two dimers together, reduces dynamics in the dimeric unit and explains why all active bacterial DHDPS enzymes to date have been shown to be homo-tetrameric. However, in this study we demonstrate for the first time that DHDPS from methicillin-resistant Staphylococcus aureus (MRSA) exists in a monomer-dimer equilibrium in solution. Fluorescence-detected analytical ultracentrifugation was employed to show that the dimerization dissociation constant of MRSA-DHDPS is 33 nm in the absence of substrates and 29 nm in the presence of (S)-aspartate semialdehyde (ASA), but is 20-fold tighter in the presence of the substrate pyruvate (1.6 nm). The MRSA-DHDPS dimer exhibits a ping-pong kinetic mechanism (k(cat)=70+/-2 s(-1), K(m)(Pyruvate)=0.11+/-0.01 mm, and K(m)(ASA)=0.22+/-0.02 mm) and shows ASA substrate inhibition with a K(si)(ASA) of 2.7+/-0.9 mm. We also demonstrate that unlike the E. coli tetramer, the MRSA-DHDPS dimer is insensitive to lysine inhibition. The near atomic resolution (1.45 A) crystal structure confirms the dimeric quaternary structure and reveals that the dimerization interface of the MRSA enzyme is more extensive in buried surface area and noncovalent contacts than the equivalent interface in tetrameric DHDPS enzymes from other bacterial species. These data provide a detailed mechanistic insight into DHDPS catalysis and the evolution of quaternary structure of this important bacterial enzyme.

Structure and evolution of a novel dimeric enzyme from a clinically important bacterial pathogen.,Burgess BR, Dobson RC, Bailey MF, Atkinson SC, Griffin MD, Jameson GB, Parker MW, Gerrard JA, Perugini MA J Biol Chem. 2008 Oct 10;283(41):27598-603. Epub 2008 Aug 5. PMID:18684709<ref>PMID:18684709</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3daq" style="background-color:#fffaf0;"></div>

==See Also==
*[[Dihydrodipicolinate synthase|Dihydrodipicolinate synthase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Staphylococcus aureus subsp. aureus MRSA252]]
[[Category: Burgess BR]]
[[Category: Dobson RCJ]]
[[Category: Gerrard JA]]
[[Category: Jameson GB]]
[[Category: Parker MW]]
[[Category: Perugini MA]]