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[[Image:1bws.jpg|left|200px]]<br /><applet load="1bws" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1bws, resolution 2.2&Aring;" />
'''CRYSTAL STRUCTURE OF GDP-4-KETO-6-DEOXY-D-MANNOSE EPIMERASE/REDUCTASE FROM ESCHERICHIA COLI A KEY ENZYME IN THE BIOSYNTHESIS OF GDP-L-FUCOSE'''<br />


==Overview==
==CRYSTAL STRUCTURE OF GDP-4-KETO-6-DEOXY-D-MANNOSE EPIMERASE/REDUCTASE FROM ESCHERICHIA COLI A KEY ENZYME IN THE BIOSYNTHESIS OF GDP-L-FUCOSE==
BACKGROUND: The process of guanosine 5'-diphosphate L-fucose, (GDP-L-fucose) biosynthesis is conserved throughout evolution from, prokaryotes to man. In animals, GDP-L-fucose is the substrate of, fucosyltransferases that participate in the biosynthesis and remodeling of, glycoconjugates, including ABH blood group and Lewis-system antigens. The, 'de novo' pathway of GDP-L-fucose biosynthesis from GDP-D-mannose involves, a GDP-D-mannose 4,6 dehydratase (GMD) and a GDP-4-keto-6-deoxy-D-mannose, epimerase/reductase (GMER). Neither of the catalytic mechanisms nor the, three-dimensional structures of the two enzymes has been elucidated yet., The severe leukocyte adhesion deficiency (LAD) type II genetic syndrome is, known to result from deficiencies in this de novo pathway. RESULTS: The, crystal structures of apo- and holo-GMER have been determined at 2.1 A and, 2.2 A resolution, respectively. Each subunit of the homodimeric (2 x 34, kDa) enzyme is composed of two domains. The N-terminal domain, a, six-stranded Rossmann fold, binds NADP+; the C-terminal domain (about 100, residues) displays an alpha/beta topology. NADP+ interacts with residues, Arg12 and Arg36 at the adenylic ribose phosphate; moreover, a protein loop, based on the Gly-X-X-Gly-X-X-Gly motif (where X is any amino acid), stabilizes binding of the coenzyme diphosphate bridge. The nicotinamide, and the connected ribose ring are located close to residues Ser107, Tyr136, and Lys140, the putative GMER active-site center. CONCLUSIONS: The GMER, fold is reminiscent of that observed for UDP-galactose epimerase (UGE), from Escherichia coli. Consideration of the enzyme fold and of its main, structural features allows assignment of GMER to the, reductase-epimerase-dehydrogenase (RED) enzyme homology superfamily, to, which short-chain dehydrogenase/reductases (SDRs) also belong. The, location of the NADP+ nicotinamide ring at an interdomain cleft is, compatible with substrate binding in the C-terminal domain.
<StructureSection load='1bws' size='340' side='right'caption='[[1bws]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 
== Structural highlights ==
==About this Structure==
<table><tr><td colspan='2'>[[1bws]] 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=1BWS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BWS FirstGlance]. <br>
1BWS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=NDP:'>NDP</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Site: <scene name='pdbsite=CAT:Catalytic+Residues'>CAT</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BWS 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=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</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=1bws FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bws OCA], [https://pdbe.org/1bws PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1bws RCSB], [https://www.ebi.ac.uk/pdbsum/1bws PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1bws ProSAT]</span></td></tr>
GDP-4-keto-6-deoxy-D-mannose epimerase/reductase from Escherichia coli, a key enzyme in the biosynthesis of GDP-L-fucose, displays the structural characteristics of the RED protein homology superfamily., Rizzi M, Tonetti M, Vigevani P, Sturla L, Bisso A, Flora AD, Bordo D, Bolognesi M, Structure. 1998 Nov 15;6(11):1453-65. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9817848 9817848]
</table>
== Function ==
[https://www.uniprot.org/uniprot/FCL_ECOLI FCL_ECOLI] Catalyzes the two-step NADP-dependent conversion of GDP-4-dehydro-6-deoxy-D-mannose to GDP-fucose, involving an epimerase and a reductase reaction.<ref>PMID:9473059</ref> <ref>PMID:10480878</ref> <ref>PMID:11021971</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/bw/1bws_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=1bws ConSurf].
<div style="clear:both"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Bolognesi, M.]]
[[Category: Bolognesi M]]
[[Category: Flora, A.D.]]
[[Category: Flora AD]]
[[Category: Rizzi, M.]]
[[Category: Rizzi M]]
[[Category: Tonetti, M.]]
[[Category: Tonetti M]]
[[Category: NDP]]
[[Category: epimerase/reductase]]
[[Category: gdp-l-fucose biosynthesis]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 09:34:09 2008''

Latest revision as of 09:39, 7 February 2024

CRYSTAL STRUCTURE OF GDP-4-KETO-6-DEOXY-D-MANNOSE EPIMERASE/REDUCTASE FROM ESCHERICHIA COLI A KEY ENZYME IN THE BIOSYNTHESIS OF GDP-L-FUCOSECRYSTAL STRUCTURE OF GDP-4-KETO-6-DEOXY-D-MANNOSE EPIMERASE/REDUCTASE FROM ESCHERICHIA COLI A KEY ENZYME IN THE BIOSYNTHESIS OF GDP-L-FUCOSE

Structural highlights

1bws is a 1 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.2Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

FCL_ECOLI Catalyzes the two-step NADP-dependent conversion of GDP-4-dehydro-6-deoxy-D-mannose to GDP-fucose, involving an epimerase and a reductase reaction.[1] [2] [3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

  1. ↑ Andrianopoulos K, Wang L, Reeves PR. Identification of the fucose synthetase gene in the colanic acid gene cluster of Escherichia coli K-12. J Bacteriol. 1998 Feb;180(4):998-1001. PMID:9473059
  2. ↑ Menon S, Stahl M, Kumar R, Xu GY, Sullivan F. Stereochemical course and steady state mechanism of the reaction catalyzed by the GDP-fucose synthetase from Escherichia coli. J Biol Chem. 1999 Sep 17;274(38):26743-50. PMID:10480878
  3. ↑ Rosano C, Bisso A, Izzo G, Tonetti M, Sturla L, De Flora A, Bolognesi M. Probing the catalytic mechanism of GDP-4-keto-6-deoxy-d-mannose Epimerase/Reductase by kinetic and crystallographic characterization of site-specific mutants. J Mol Biol. 2000 Oct 13;303(1):77-91. PMID:11021971 doi:10.1006/jmbi.2000.4106

1bws, resolution 2.20Å

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