View source for 6ppw


==Crystal structure of NeuB, an N-acetylneuraminate synthase from Neisseria meningitidis, in complex with magnesium and malate==
<StructureSection load='6ppw' size='340' side='right'caption='[[6ppw]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ppw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Neisseria_meningitidis_serogroup_B Neisseria meningitidis serogroup B]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2zdr 2zdr]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PPW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PPW 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]] 1.85&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MLT:D-MALATE'>MLT</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=6ppw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ppw OCA], [https://pdbe.org/6ppw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ppw RCSB], [https://www.ebi.ac.uk/pdbsum/6ppw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ppw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/H2VFG5_NEIMI H2VFG5_NEIMI] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
NeuB is a bacterial sialic acid synthase used by neuroinvasive bacteria to synthesize &lt;i&gt;N&lt;/i&gt;-acetylneuraminate (NeuNAc), helping them to evade the host immune system. NeuNAc oxime is a potent slow-binding NeuB inhibitor. It dissociated too slowly to be detected experimentally, with initial estimates of its residence time in the active site being &gt; 47 days. This is longer than the lifetime of a typical bacterial cell, meaning that inhibition is effectively irreversible. Inhibition data fitted well to a model that included a pre-equilibration step with &lt;i&gt;K&lt;/i&gt;&lt;sub&gt;i&lt;/sub&gt; = 36 muM, followed by effectively irreversible conversion to an E*.I complex, with &lt;i&gt;k&lt;/i&gt;&lt;sub&gt;2&lt;\sub&gt; = 5.6 x 10&lt;sup&gt;-5&lt;/sup&gt; s&lt;sup&gt;-1&lt;/sup&gt;. Thus, the inhibitor is able to subvert ligand release and achieve extraordinary residence times in spite of a relatively modest initial dissociation constant. The crystal structure showed the oxime functional group occupying the phosphate binding site normally occupied by the substrate PEP and the tetrahedral intermediate. There was a ~10% residual rate at high inhibitor concentrations regardless of how long NeuB and NeuNAc oxime were pre-incubated together. However, complete inhibition was achieved by incubating NeuNAc oxime with actively catalyzing enzyme. This requirement for the enzyme to be actively turning over in order for the inhibitor to bind to the second subunit demonstrated an important role for inter-subunit communication in the inhibitory mechanism.

NeuNAc oxime: A slow-binding and effectively irreversible inhibitor of the sialic acid synthase NeuB.,Popovic V, Morrison E, Rosanally AZ, Balachandran N, Senson AW, Szabla R, Junop MS, Berti PJ Biochemistry. 2019 Sep 24. doi: 10.1021/acs.biochem.9b00654. PMID:31549502<ref>PMID:31549502</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ppw" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Neisseria meningitidis serogroup B]]
[[Category: Berti PJ]]
[[Category: Junop MS]]
[[Category: Rosanally AZ]]