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| <StructureSection load='1xuu' size='340' side='right'caption='[[1xuu]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='1xuu' size='340' side='right'caption='[[1xuu]], [[Resolution|resolution]] 1.90Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[1xuu]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"diplokokkus_intracellularis_meningitidis"_(sic)_weichselbaum_1887 "diplokokkus intracellularis meningitidis" (sic) weichselbaum 1887]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XUU OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1XUU FirstGlance]. <br> | | <table><tr><td colspan='2'>[[1xuu]] 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=1XUU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XUU FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MLT:D-MALATE'>MLT</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1xuz|1xuz]]</div></td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MLT:D-MALATE'>MLT</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">neuB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=487 "Diplokokkus intracellularis meningitidis" (sic) Weichselbaum 1887])</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=1xuu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xuu OCA], [https://pdbe.org/1xuu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xuu RCSB], [https://www.ebi.ac.uk/pdbsum/1xuu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xuu ProSAT]</span></td></tr> |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1xuu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xuu OCA], [http://pdbe.org/1xuu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1xuu RCSB], [http://www.ebi.ac.uk/pdbsum/1xuu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1xuu ProSAT]</span></td></tr> | |
| </table> | | </table> |
| | == Function == |
| | [https://www.uniprot.org/uniprot/Q57265_NEIME Q57265_NEIME] |
| == Evolutionary Conservation == | | == Evolutionary Conservation == |
| [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| </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=1xuu ConSurf]. | | </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=1xuu ConSurf]. |
| <div style="clear:both"></div> | | <div style="clear:both"></div> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
| |
| 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.
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| 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:15516336<ref>PMID:15516336</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 1xuu" style="background-color:#fffaf0;"></div>
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| == References ==
| |
| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Gilbert, M]] | | [[Category: Neisseria meningitidis]] |
| [[Category: Gunawan, J]] | | [[Category: Gilbert M]] |
| [[Category: Lovering, A L]] | | [[Category: Gunawan J]] |
| [[Category: Simard, D]] | | [[Category: Lovering AL]] |
| [[Category: Strynadka, N C]] | | [[Category: Simard D]] |
| [[Category: Tanner, M E]] | | [[Category: Strynadka NC]] |
| [[Category: Wakarchuk, W W]] | | [[Category: Tanner ME]] |
| [[Category: Antifreeze-like domain]]
| | [[Category: Wakarchuk WW]] |
| [[Category: Biosynthetic protein]]
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| [[Category: Domain-swapped dimer]]
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| [[Category: Tim barrel]]
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