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New page: left|200px<br /><applet load="1xuz" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xuz, resolution 2.2Å" /> '''Crystal structure ana...
 
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[[Image:1xuz.jpg|left|200px]]<br /><applet load="1xuz" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1xuz, resolution 2.2&Aring;" />
'''Crystal structure analysis of sialic acid synthase (NeuB)from Neisseria meningitidis, bound to Mn2+, Phosphoenolpyruvate, and N-acetyl mannosaminitol'''<br />


==Overview==
==Crystal structure analysis of sialic acid synthase (NeuB)from Neisseria meningitidis, bound to Mn2+, Phosphoenolpyruvate, and N-acetyl mannosaminitol==
In Neisseria meningitidis and related bacterial pathogens, sialic acids, play critical roles in mammalian cell immunity evasion and are synthesized, by a conserved enzymatic pathway that includes sialic acid synthase (NeuB, SiaC, or SynC). NeuB catalyzes the condensation of phosphoenolpyruvate, (PEP) and N-acetylmannosamine, directly forming N-acetylneuraminic acid, (or sialic acid). In this paper we report the development of a coupled, assay to monitor NeuB reaction kinetics and an 18O-labeling study that, demonstrates the synthase operates via a C-O bond cleavage mechanism. We, also report the first structure of a sialic acid synthase, that of NeuB, revealing a unique domain-swapped homodimer architecture consisting of a, (beta/alpha)8 barrel (TIM barrel)-type fold at the N-terminal end and a, domain with high sequence identity and structural similarity to the ice, binding type III antifreeze proteins at the C-terminal end of the enzyme., We have determined the structures of NeuB in the malate-bound form and, with bound PEP and the substrate analog N-acetylmannosaminitol to 1.9 and, 2.2 A resolution, respectively. Typical of other TIM barrel proteins, the, active site of NeuB is located in a cavity at the C-terminal end of the, barrel; however, the positioning of the swapped antifreeze-like domain, from the adjacent monomer provides key residues for hydrogen bonding with, substrates in the active site of NeuB, a structural feature that leads to, distinct modes of substrate binding from other PEP-utilizing enzymes that, lack an analogous antifreeze-like domain. Our observation of a direct, interaction between a highly ordered manganese and the, N-acetylmannosaminitol in the NeuB active site also suggests an essential, role for the ion as an electrophilic catalyst that activates the, N-acetylmannosamine carbonyl to the addition of PEP.
<StructureSection load='1xuz' size='340' side='right'caption='[[1xuz]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 
== Structural highlights ==
==About this Structure==
<table><tr><td colspan='2'>[[1xuz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Neisseria_meningitidis Neisseria meningitidis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XUZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XUZ FirstGlance]. <br>
1XUZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Neisseria_meningitidis Neisseria meningitidis] with MMN, MN and PEP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1XUZ OCA].  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
 
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MMN:5-DEOXY-5-{[(1S)-1-HYDROXYETHYL]AMINO}-D-GLUCITOL'>MMN</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PEP:PHOSPHOENOLPYRUVATE'>PEP</scene></td></tr>
==Reference==
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1xuz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xuz OCA], [https://pdbe.org/1xuz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xuz RCSB], [https://www.ebi.ac.uk/pdbsum/1xuz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xuz ProSAT]</span></td></tr>
Structural and mechanistic analysis of sialic acid synthase NeuB from Neisseria meningitidis in complex with Mn2+, phosphoenolpyruvate, and N-acetylmannosaminitol., Gunawan J, Simard D, Gilbert M, Lovering AL, Wakarchuk WW, Tanner ME, Strynadka NC, J Biol Chem. 2005 Feb 4;280(5):3555-63. Epub 2004 Oct 29. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15516336 15516336]
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q57265_NEIME Q57265_NEIME]
== 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/xu/1xuz_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=1xuz ConSurf].
<div style="clear:both"></div>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Neisseria meningitidis]]
[[Category: Neisseria meningitidis]]
[[Category: Single protein]]
[[Category: Gilbert M]]
[[Category: Gilbert, M.]]
[[Category: Gunawan J]]
[[Category: Gunawan, J.]]
[[Category: Lovering AL]]
[[Category: Lovering, A.L.]]
[[Category: Simard D]]
[[Category: Simard, D.]]
[[Category: Strynadka NC]]
[[Category: Strynadka, N.C.]]
[[Category: Tanner ME]]
[[Category: Tanner, M.E.]]
[[Category: Wakarchuk WW]]
[[Category: Wakarchuk, W.W.]]
[[Category: MMN]]
[[Category: MN]]
[[Category: PEP]]
[[Category: antifreeze-like domain]]
[[Category: domain-swapped dimer]]
[[Category: tim barrel]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 25 02:58:24 2007''

Latest revision as of 08:53, 14 February 2024

Crystal structure analysis of sialic acid synthase (NeuB)from Neisseria meningitidis, bound to Mn2+, Phosphoenolpyruvate, and N-acetyl mannosaminitol

1xuz, resolution 2.20Å

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