2udp
From Proteopedia
(New page: 200px<br /><applet load="2udp" size="450" color="white" frame="true" align="right" spinBox="true" caption="2udp, resolution 1.80Å" /> '''UDP-GALACTOSE 4-EPIM...) |
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| - | [[Image:2udp.jpg|left|200px]]<br /><applet load="2udp" size=" | + | [[Image:2udp.jpg|left|200px]]<br /><applet load="2udp" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2udp, resolution 1.80Å" /> | caption="2udp, resolution 1.80Å" /> | ||
'''UDP-GALACTOSE 4-EPIMERASE COMPLEXED WITH UDP-PHENOL'''<br /> | '''UDP-GALACTOSE 4-EPIMERASE COMPLEXED WITH UDP-PHENOL'''<br /> | ||
==Overview== | ==Overview== | ||
| - | UDP-galactose 4-epimerase from Escherichia coli catalyzes the | + | UDP-galactose 4-epimerase from Escherichia coli catalyzes the interconversion of UDP-glucose and UDP-galactose. In recent years, the enzyme has been the subject of intensive investigation due in part to its ability to facilitate nonstereospecific hydride transfer between beta-NADH and a 4-keto hexopyranose intermediate. The first molecular model of the epimerase from E. coli was solved to 2.5 A resolution with crystals grown in the presence of a substrate analogue, UDP-phenol (Bauer AJ, Rayment I, Frey PA, Holden HM, 1992, Proteins Struct Funct Genet 12:372-381). There were concerns at the time that the inhibitor did not adequately mimic the sugar moiety of a true substrate. Here we describe the high-resolution X-ray crystal structure of the ternary complex of UDP-galactose 4-epimerase with NADH and UDP-phenol. The model was refined to 1.8 A resolution with a final overall R-factor of 18.6%. This high-resolution structural analysis demonstrates that the original concerns were unfounded and that, in fact, UDP-phenol and UDP-glucose bind similarly. The carboxamide groups of the dinucleotides, in both subunits, are displaced significantly from the planes of the nicotinamide rings by hydrogen bonding interactions with Ser 124 and Tyr 149. UDP-galactose 4-epimerase belongs to a family of enzymes known as the short-chain dehydrogenases, which contain a characteristic Tyr-Lys couple thought to be important for catalysis. The epimerase/NADH/UDP-phenol model presented here represents a well-defined ternary complex for this family of proteins and, as such, provides important information regarding the possible role of the Tyr-Lys couple in the reaction mechanism. |
==About this Structure== | ==About this Structure== | ||
| - | 2UDP 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, UPP and EDO as [http://en.wikipedia.org/wiki/ligands ligands]. This structure | + | 2UDP 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=UPP:'>UPP</scene> and <scene name='pdbligand=EDO:'>EDO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 1UDP. 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=2UDP OCA]. |
==Reference== | ==Reference== | ||
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[[Category: UDP-glucose 4-epimerase]] | [[Category: UDP-glucose 4-epimerase]] | ||
[[Category: Gulick, A.]] | [[Category: Gulick, A.]] | ||
| - | [[Category: Holden, H | + | [[Category: Holden, H M.]] |
| - | [[Category: Thoden, J | + | [[Category: Thoden, J B.]] |
[[Category: EDO]] | [[Category: EDO]] | ||
[[Category: NA]] | [[Category: NA]] | ||
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[[Category: udp-galactose]] | [[Category: udp-galactose]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:50:14 2008'' |
Revision as of 16:50, 21 February 2008
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UDP-GALACTOSE 4-EPIMERASE COMPLEXED WITH UDP-PHENOL
Overview
UDP-galactose 4-epimerase from Escherichia coli catalyzes the interconversion of UDP-glucose and UDP-galactose. In recent years, the enzyme has been the subject of intensive investigation due in part to its ability to facilitate nonstereospecific hydride transfer between beta-NADH and a 4-keto hexopyranose intermediate. The first molecular model of the epimerase from E. coli was solved to 2.5 A resolution with crystals grown in the presence of a substrate analogue, UDP-phenol (Bauer AJ, Rayment I, Frey PA, Holden HM, 1992, Proteins Struct Funct Genet 12:372-381). There were concerns at the time that the inhibitor did not adequately mimic the sugar moiety of a true substrate. Here we describe the high-resolution X-ray crystal structure of the ternary complex of UDP-galactose 4-epimerase with NADH and UDP-phenol. The model was refined to 1.8 A resolution with a final overall R-factor of 18.6%. This high-resolution structural analysis demonstrates that the original concerns were unfounded and that, in fact, UDP-phenol and UDP-glucose bind similarly. The carboxamide groups of the dinucleotides, in both subunits, are displaced significantly from the planes of the nicotinamide rings by hydrogen bonding interactions with Ser 124 and Tyr 149. UDP-galactose 4-epimerase belongs to a family of enzymes known as the short-chain dehydrogenases, which contain a characteristic Tyr-Lys couple thought to be important for catalysis. The epimerase/NADH/UDP-phenol model presented here represents a well-defined ternary complex for this family of proteins and, as such, provides important information regarding the possible role of the Tyr-Lys couple in the reaction mechanism.
About this Structure
2UDP is a Single protein structure of sequence from Escherichia coli with , , and as ligands. This structure supersedes the now removed PDB entry 1UDP. Active as UDP-glucose 4-epimerase, with EC number 5.1.3.2 Full crystallographic information is available from OCA.
Reference
High-resolution X-ray structure of UDP-galactose 4-epimerase complexed with UDP-phenol., Thoden JB, Frey PA, Holden HM, Protein Sci. 1996 Nov;5(11):2149-61. PMID:8931134
Page seeded by OCA on Thu Feb 21 18:50:14 2008
Categories: Escherichia coli | Single protein | UDP-glucose 4-epimerase | Gulick, A. | Holden, H M. | Thoden, J B. | EDO | NA | NAD | UPP | Epimerase | Galactose metabolism | Isomerase | Udp-galactose
