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| - | [[Image:1db3.gif|left|200px]] | |
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| - | <!--
| + | ==E.COLI GDP-MANNOSE 4,6-DEHYDRATASE== |
| - | The line below this paragraph, containing "STRUCTURE_1db3", creates the "Structure Box" on the page.
| + | <StructureSection load='1db3' size='340' side='right'caption='[[1db3]], [[Resolution|resolution]] 2.30Å' scene=''> |
| - | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
| - | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[1db3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DB3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DB3 FirstGlance]. <br> |
| - | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</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=1db3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1db3 OCA], [https://pdbe.org/1db3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1db3 RCSB], [https://www.ebi.ac.uk/pdbsum/1db3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1db3 ProSAT]</span></td></tr> |
| - | {{STRUCTURE_1db3| PDB=1db3 | SCENE= }}
| + | </table> |
| - | | + | == Function == |
| - | '''E.COLI GDP-MANNOSE 4,6-DEHYDRATASE'''
| + | [https://www.uniprot.org/uniprot/GM4D_ECOLI GM4D_ECOLI] |
| - | | + | == Evolutionary Conservation == |
| - | | + | [[Image:Consurf_key_small.gif|200px|right]] |
| - | ==Overview== | + | Check<jmol> |
| - | Background: GDP-mannose 4,6 dehydratase (GMD) catalyzes the conversion of GDP-(D)-mannose to GDP-4-keto, 6-deoxy-(D)-mannose. This is the first and regulatory step in the de novo biosynthesis of GDP-(L)-fucose. Fucose forms part of a number of glycoconjugates, including the ABO blood groups and the selectin ligand sialyl Lewis X. Defects in GDP-fucose metabolism have been linked to leukocyte adhesion deficiency type II (LADII). Results: The structure of the GDP-mannose 4,6 dehydratase apo enzyme has been determined and refined using data to 2.3 A resolution. GMD is a homodimeric protein with each monomer composed of two domains. The larger N-terminal domain binds the NADP(H) cofactor in a classical Rossmann fold and the C-terminal domain harbors the sugar-nucleotide binding site. We have determined the GMD dissociation constants for NADP, NADPH and GDP-mannose. Each GMD monomer binds one cofactor and one substrate molecule, suggesting that both subunits are catalytically competent. GDP-fucose acts as a competitive inhibitor, suggesting that it binds to the same site as GDP-mannose, providing a mechanism for the feedback inhibition of fucose biosynthesis. Conclusions: The X-ray structure of GMD reveals that it is a member of the short-chain dehydrogenase/reductase (SDR) family of proteins. We have modeled the binding of NADP and GDP-mannose to the enzyme and mutated four of the active-site residues to determine their function. The combined modeling and mutagenesis data suggests that at position 133 threonine substitutes serine as part of the serine-tyrosine-lysine catalytic triad common to the SDR family and Glu 135 functions as an active-site base.
| + | <jmolCheckbox> |
| - | | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/db/1db3_consurf.spt"</scriptWhenChecked> |
| - | ==About this Structure== | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| - | 1DB3 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DB3 OCA].
| + | <text>to colour the structure by Evolutionary Conservation</text> |
| - | | + | </jmolCheckbox> |
| - | ==Reference== | + | </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=1db3 ConSurf]. |
| - | Structural and kinetic analysis of Escherichia coli GDP-mannose 4,6 dehydratase provides insights into the enzyme's catalytic mechanism and regulation by GDP-fucose., Somoza JR, Menon S, Schmidt H, Joseph-McCarthy D, Dessen A, Stahl ML, Somers WS, Sullivan FX, Structure. 2000 Feb 15;8(2):123-35. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10673432 10673432]
| + | <div style="clear:both"></div> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Escherichia coli]] | | [[Category: Escherichia coli]] |
| - | [[Category: GDP-mannose 4,6-dehydratase]] | + | [[Category: Large Structures]] |
| - | [[Category: Single protein]]
| + | [[Category: Menon S]] |
| - | [[Category: Menon, S.]] | + | [[Category: Somers WS]] |
| - | [[Category: Somers, W S.]] | + | [[Category: Somoza JR]] |
| - | [[Category: Somoza, J R.]] | + | [[Category: Sullivan FX]] |
| - | [[Category: Sullivan, F X.]] | + | |
| - | [[Category: Dehydratase]]
| + | |
| - | [[Category: Gdp-fucose]]
| + | |
| - | [[Category: Gdp-mannose]]
| + | |
| - | [[Category: Nadp]]
| + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 13:38:59 2008''
| + | |
