1e7r
From Proteopedia
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|PDB= 1e7r |SIZE=350|CAPTION= <scene name='initialview01'>1e7r</scene>, resolution 1.6Å | |PDB= 1e7r |SIZE=350|CAPTION= <scene name='initialview01'>1e7r</scene>, resolution 1.6Å | ||
|SITE= <scene name='pdbsite=AC1:Nap+Binding+Site+For+Chain+A'>AC1</scene>, <scene name='pdbsite=AC2:Uvw+Binding+Site+For+Chain+A'>AC2</scene> and <scene name='pdbsite=CAT:Catalytic+Triad+Residue+GLU+A136+Is+Mutated+The+Native+B+...'>CAT</scene> | |SITE= <scene name='pdbsite=AC1:Nap+Binding+Site+For+Chain+A'>AC1</scene>, <scene name='pdbsite=AC2:Uvw+Binding+Site+For+Chain+A'>AC2</scene> and <scene name='pdbsite=CAT:Catalytic+Triad+Residue+GLU+A136+Is+Mutated+The+Native+B+...'>CAT</scene> | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene>, <scene name='pdbligand=UVW:ACETYLPHOSPHATE'>UVW</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1e7r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e7r OCA], [http://www.ebi.ac.uk/pdbsum/1e7r PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1e7r RCSB]</span> | ||
}} | }} | ||
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[[Category: Izzo, G.]] | [[Category: Izzo, G.]] | ||
[[Category: Rosano, C.]] | [[Category: Rosano, C.]] | ||
| - | [[Category: NAP]] | ||
| - | [[Category: SO4]] | ||
| - | [[Category: TRS]] | ||
| - | [[Category: UVW]] | ||
[[Category: epimerase/reductase]] | [[Category: epimerase/reductase]] | ||
[[Category: red]] | [[Category: red]] | ||
[[Category: sdr]] | [[Category: sdr]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:57:03 2008'' |
Revision as of 16:57, 30 March 2008
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| , resolution 1.6Å | |||||||
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| Sites: | , and | ||||||
| Ligands: | , , , | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
GDP 4-KETO-6-DEOXY-D-MANNOSE EPIMERASE REDUCTASE Y136E
Overview
GDP-4-keto-6-deoxy-d-mannose epimerase/reductase is a bifunctional enzyme responsible for the last step in the biosynthesis of GDP-l-fucose, the substrate of fucosyl transferases. Several cell-surface antigens, including the leukocyte Lewis system and cell-surface antigens in pathogenic bacteria, depend on the availability of GDP-l-fucose for their expression. Therefore, the enzyme is a potential target for therapy in pathological states depending on selectin-mediated cell-to-cell interactions. Previous crystallographic investigations have shown that GDP-4-keto-6-deoxy-d-mannose epimerase/reductase belongs to the short-chain dehydrogenase/reductase protein homology family. The enzyme active-site region is at the interface of an N-terminal NADPH-binding domain and a C-terminal domain, held to bind the substrate. The design, expression and functional characterization of seven site-specific mutant forms of GDP-4-keto-6-deoxy-d-mannose epimerase/reductase are reported here. In parallel, the crystal structures of the native holoenzyme and of three mutants (Ser107Ala, Tyr136Glu and Lys140Arg) have been investigated and refined at 1. 45-1.60 A resolution, based on synchrotron data (R-factors range between 12.6 % and 13.9 %). The refined protein models show that besides the active-site residues Ser107, Tyr136 and Lys140, whose mutations impair the overall enzymatic activity and may affect the coenzyme binding mode, side-chains capable of proton exchange, located around the expected substrate (GDP-4-keto-6-deoxy-d-mannose) binding pocket, are selectively required during the epimerization and reduction steps. Among these, Cys109 and His179 may play a primary role in proton exchange between the enzyme and the epimerization catalytic intermediates. Finally, the additional role of mutated active-site residues involved in substrate recognition and in enzyme stability has been analyzed.
About this Structure
1E7R is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
Probing the catalytic mechanism of GDP-4-keto-6-deoxy-d-mannose Epimerase/Reductase by kinetic and crystallographic characterization of site-specific mutants., Rosano C, Bisso A, Izzo G, Tonetti M, Sturla L, De Flora A, Bolognesi M, J Mol Biol. 2000 Oct 13;303(1):77-91. PMID:11021971
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