1udc: Difference between revisions

Revision as of 16:23, 21 February 2008

STRUCTURE OF UDP-GALACTOSE-4-EPIMERASE COMPLEXED WITH UDP-MANNOSE

OverviewOverview

UDP-galactose 4-epimerase from Escherichia coli catalyzes the interconversion of UDP-galactose and UDP-glucose through the transient reduction of the tightly bound cofactor NAD+. The enzyme is unique among the NAD+-dependent enzymes in that it promotes stereospecific reduction of the cofactor but nonstereospecific hydride return during normal catalysis. In addition to hydride transfer, the reaction mechanism of epimerase involves two key features: the abstraction of a proton from the 4'-hydroxyl group of glucose or galactose by an active site base and the rotation of a 4-ketopyranose intermediate in the active site pocket. To address the second issue of movement within the active site, the X-ray structures of reduced epimerase complexed with UDP-mannose, UDP-4-deoxy-4-fluoro-alpha-D-galactose, or UDP-4-deoxy-4-fluoro-alpha-D-glucose have been determined and refined to 1.65, 1.8, and 1.65 A resolution, respectively. A comparison of these models to that of the previously determined epimerase/NADH/UDP-glucose abortive complex reveals that the active site accommodates the various sugars by simple rearrangements of water molecules rather than by large changes in side chain conformations. In fact, the polypeptide chains for all of the epimerase/NADH/UDP-sugar complexes studied thus far are remarkably similar and can be superimposed with root-mean-square deviations of not greater than 0.24 A. The only significant differences between the various enzyme/UDP-sugar models occur in two of the dihedral angles defining the conformation of the UDP-sugar ligands.

About this StructureAbout this Structure

1UDC is a Single protein structure of sequence from Escherichia coli with , , , and as ligands. Active as UDP-glucose 4-epimerase, with EC number 5.1.3.2 Full crystallographic information is available from OCA.

ReferenceReference

Structural analysis of UDP-sugar binding to UDP-galactose 4-epimerase from Escherichia coli., Thoden JB, Hegeman AD, Wesenberg G, Chapeau MC, Frey PA, Holden HM, Biochemistry. 1997 May 27;36(21):6294-304. PMID:9174344

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-[[Image:1udc.jpg|left|200px]]<br /><applet load="1udc" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1udc.jpg|left|200px]]<br /><applet load="1udc" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1udc, resolution 1.65&Aring;" />
 '''STRUCTURE OF UDP-GALACTOSE-4-EPIMERASE COMPLEXED WITH UDP-MANNOSE'''<br />
 ==Overview==
-UDP-galactose 4-epimerase from Escherichia coli catalyzes the, interconversion of UDP-galactose and UDP-glucose through the transient, reduction of the tightly bound cofactor NAD+. The enzyme is unique among, the NAD+-dependent enzymes in that it promotes stereospecific reduction of, the cofactor but nonstereospecific hydride return during normal catalysis., In addition to hydride transfer, the reaction mechanism of epimerase, involves two key features: the abstraction of a proton from the, 4'-hydroxyl group of glucose or galactose by an active site base and the, rotation of a 4-ketopyranose intermediate in the active site pocket. To, address the second issue of movement within the active site, the X-ray, structures of reduced epimerase complexed with UDP-mannose, UDP-4-deoxy-4-fluoro-alpha-D-galactose, or, UDP-4-deoxy-4-fluoro-alpha-D-glucose have been determined and refined to, 1.65, 1.8, and 1.65 A resolution, respectively. A comparison of these, models to that of the previously determined epimerase/NADH/UDP-glucose, abortive complex reveals that the active site accommodates the various, sugars by simple rearrangements of water molecules rather than by large, changes in side chain conformations. In fact, the polypeptide chains for, all of the epimerase/NADH/UDP-sugar complexes studied thus far are, remarkably similar and can be superimposed with root-mean-square, deviations of not greater than 0.24 A. The only significant differences, between the various enzyme/UDP-sugar models occur in two of the dihedral, angles defining the conformation of the UDP-sugar ligands.
+UDP-galactose 4-epimerase from Escherichia coli catalyzes the interconversion of UDP-galactose and UDP-glucose through the transient reduction of the tightly bound cofactor NAD+. The enzyme is unique among the NAD+-dependent enzymes in that it promotes stereospecific reduction of the cofactor but nonstereospecific hydride return during normal catalysis. In addition to hydride transfer, the reaction mechanism of epimerase involves two key features: the abstraction of a proton from the 4'-hydroxyl group of glucose or galactose by an active site base and the rotation of a 4-ketopyranose intermediate in the active site pocket. To address the second issue of movement within the active site, the X-ray structures of reduced epimerase complexed with UDP-mannose, UDP-4-deoxy-4-fluoro-alpha-D-galactose, or UDP-4-deoxy-4-fluoro-alpha-D-glucose have been determined and refined to 1.65, 1.8, and 1.65 A resolution, respectively. A comparison of these models to that of the previously determined epimerase/NADH/UDP-glucose abortive complex reveals that the active site accommodates the various sugars by simple rearrangements of water molecules rather than by large changes in side chain conformations. In fact, the polypeptide chains for all of the epimerase/NADH/UDP-sugar complexes studied thus far are remarkably similar and can be superimposed with root-mean-square deviations of not greater than 0.24 A. The only significant differences between the various enzyme/UDP-sugar models occur in two of the dihedral angles defining the conformation of the UDP-sugar ligands.
 ==About this Structure==
-UDC 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 NA, NAD, UFM, PGE and EDO as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/UDP-glucose_4-epimerase UDP-glucose 4-epimerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.1.3.2 5.1.3.2] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1UDC OCA].
+UDC 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=NA:'>NA</scene>, <scene name='pdbligand=NAD:'>NAD</scene>, <scene name='pdbligand=UFM:'>UFM</scene>, <scene name='pdbligand=PGE:'>PGE</scene> and <scene name='pdbligand=EDO:'>EDO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/UDP-glucose_4-epimerase UDP-glucose 4-epimerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.1.3.2 5.1.3.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UDC OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Single protein]]
 [[Category: UDP-glucose 4-epimerase]]
-[[Category: Holden, H.M.]]
+[[Category: Holden, H M.]]
-[[Category: Thoden, J.B.]]
+[[Category: Thoden, J B.]]
 [[Category: EDO]]
 [[Category: NA]]
@@ Line 25: / Line 25: @@
 [[Category: udp-galactose]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 04:02:18 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:23:20 2008''