1e7q: Difference between revisions
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[[Image:1e7q.jpg|left|200px]]<br /><applet load="1e7q" size=" | [[Image:1e7q.jpg|left|200px]]<br /><applet load="1e7q" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1e7q, resolution 1.6Å" /> | caption="1e7q, resolution 1.6Å" /> | ||
'''GDP 4-KETO-6-DEOXY-D-MANNOSE EPIMERASE REDUCTASE S107A'''<br /> | '''GDP 4-KETO-6-DEOXY-D-MANNOSE EPIMERASE REDUCTASE S107A'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
1E7Q 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 SO4, NAP, UVW and TRS as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Sites: <scene name='pdbsite=AC1:Nap Binding Site, Residue Ala107 Is Mutat The Native Bei ...'>AC1</scene> and <scene name='pdbsite=AC2:Uvw Binding Site For Chain A'>AC2</scene>. Full crystallographic information is available from [http:// | 1E7Q 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=SO4:'>SO4</scene>, <scene name='pdbligand=NAP:'>NAP</scene>, <scene name='pdbligand=UVW:'>UVW</scene> and <scene name='pdbligand=TRS:'>TRS</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Sites: <scene name='pdbsite=AC1:Nap+Binding+Site,+Residue+Ala107+Is+Mutat+The+Native+Bei+...'>AC1</scene> and <scene name='pdbsite=AC2:Uvw+Binding+Site+For+Chain+A'>AC2</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E7Q OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: sdr]] | [[Category: sdr]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 09:38:00 2008'' | ||
Revision as of 10:38, 3 February 2008
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GDP 4-KETO-6-DEOXY-D-MANNOSE EPIMERASE REDUCTASE S107A
OverviewOverview
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 StructureAbout this Structure
1E7Q is a Single protein structure of sequence from Escherichia coli with , , and as ligands. Known structural/functional Sites: and . Full crystallographic information is available from OCA.
ReferenceReference
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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