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< | ==Crystal structure of UDP-GlcNAc inverting 4,6-dehydratase in complex with NADPH and UDP-GlcNAc== | ||
<StructureSection load='2gn4' size='340' side='right'caption='[[2gn4]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2gn4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Helicobacter_pylori Helicobacter pylori]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GN4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GN4 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]] 1.9Å</td></tr> | |||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=UD1:URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE'>UD1</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=2gn4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gn4 OCA], [https://pdbe.org/2gn4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gn4 RCSB], [https://www.ebi.ac.uk/pdbsum/2gn4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gn4 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PSEB_HELPY PSEB_HELPY] Catalyzes the first step in the biosynthesis of pseudaminic acid, a sialic-acid-like sugar that is used to modify flagellin. Has both C6 dehydratase and C5 epimerase activities that result in the production of both UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-4-hexulose and UDP-2-acetamido-2,6-dideoxy-alpha-D-xylo-4-hexulose.<ref>PMID:16286454</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/gn/2gn4_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=2gn4 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
FlaA1 from the human pathogen Helicobacter pylori is an enzyme involved in saccharide biosynthesis that has been shown to be essential for pathogenicity. Here we present five crystal structures of FlaA1 in the presence of substrate, inhibitors, and bound cofactor, with resolutions ranging from 2.8 to 1.9 A. These structures reveal that the enzyme is a novel member of the short-chain dehydrogenase/reductase superfamily. Additional electron microscopy studies show the enzyme to possess a hexameric doughnut-shaped quaternary structure. NMR analyses of "real time" enzyme-substrate reactions indicate that FlaA1 is a UDP-GlcNAc-inverting 4,6-dehydratase, suggesting that the enzyme catalyzes the first step in the biosynthetic pathway of a pseudaminic acid derivative, which is implicated in protein glycosylation. Guided by evidence from site-directed mutagenesis and computational simulations, a three-step reaction mechanism is proposed that involves Lys-133 functioning as both a catalytic acid and base. | |||
Structural studies of FlaA1 from Helicobacter pylori reveal the mechanism for inverting 4,6-dehydratase activity.,Ishiyama N, Creuzenet C, Miller WL, Demendi M, Anderson EM, Harauz G, Lam JS, Berghuis AM J Biol Chem. 2006 Aug 25;281(34):24489-95. Epub 2006 May 1. PMID:16651261<ref>PMID:16651261</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2gn4" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
== | |||
< | |||
[[Category: Helicobacter pylori]] | [[Category: Helicobacter pylori]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Berghuis AM]] | ||
[[Category: | [[Category: Creuzenet C]] | ||
[[Category: | [[Category: Ishiyama N]] | ||
[[Category: | [[Category: Lam JS]] | ||
Latest revision as of 12:44, 30 August 2023
Crystal structure of UDP-GlcNAc inverting 4,6-dehydratase in complex with NADPH and UDP-GlcNAcCrystal structure of UDP-GlcNAc inverting 4,6-dehydratase in complex with NADPH and UDP-GlcNAc
Structural highlights
FunctionPSEB_HELPY Catalyzes the first step in the biosynthesis of pseudaminic acid, a sialic-acid-like sugar that is used to modify flagellin. Has both C6 dehydratase and C5 epimerase activities that result in the production of both UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-4-hexulose and UDP-2-acetamido-2,6-dideoxy-alpha-D-xylo-4-hexulose.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedFlaA1 from the human pathogen Helicobacter pylori is an enzyme involved in saccharide biosynthesis that has been shown to be essential for pathogenicity. Here we present five crystal structures of FlaA1 in the presence of substrate, inhibitors, and bound cofactor, with resolutions ranging from 2.8 to 1.9 A. These structures reveal that the enzyme is a novel member of the short-chain dehydrogenase/reductase superfamily. Additional electron microscopy studies show the enzyme to possess a hexameric doughnut-shaped quaternary structure. NMR analyses of "real time" enzyme-substrate reactions indicate that FlaA1 is a UDP-GlcNAc-inverting 4,6-dehydratase, suggesting that the enzyme catalyzes the first step in the biosynthetic pathway of a pseudaminic acid derivative, which is implicated in protein glycosylation. Guided by evidence from site-directed mutagenesis and computational simulations, a three-step reaction mechanism is proposed that involves Lys-133 functioning as both a catalytic acid and base. Structural studies of FlaA1 from Helicobacter pylori reveal the mechanism for inverting 4,6-dehydratase activity.,Ishiyama N, Creuzenet C, Miller WL, Demendi M, Anderson EM, Harauz G, Lam JS, Berghuis AM J Biol Chem. 2006 Aug 25;281(34):24489-95. Epub 2006 May 1. PMID:16651261[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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