1ll3
From Proteopedia
(New page: 200px<br /><applet load="1ll3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ll3, resolution 1.9Å" /> '''Crystal Structure of ...) |
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| - | [[Image:1ll3.gif|left|200px]]<br /><applet load="1ll3" size=" | + | [[Image:1ll3.gif|left|200px]]<br /><applet load="1ll3" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ll3, resolution 1.9Å" /> | caption="1ll3, resolution 1.9Å" /> | ||
'''Crystal Structure of Rabbit Muscle Glycogenin'''<br /> | '''Crystal Structure of Rabbit Muscle Glycogenin'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Glycogen is an important storage reserve of glucose present in many | + | Glycogen is an important storage reserve of glucose present in many organisms, from bacteria to humans. Its biosynthesis is initiated by a specialized protein, glycogenin, which has the unusual property of transferring glucose from UDP-glucose to form an oligosaccharide covalently attached to itself at Tyr194. Glycogen synthase and the branching enzyme complete the synthesis of the polysaccharide. The structure of glycogenin was solved in two different crystal forms. Tetragonal crystals contained a pentamer of dimers in the asymmetric unit arranged in an improper non-crystallographic 10-fold relationship, and orthorhombic crystals contained a monomer in the asymmetric unit that is arranged about a 2-fold crystallographic axis to form a dimer. The structure was first solved to 3.4 A using the tetragonal crystal form and a three-wavelength Se-Met multi-wavelength anomalous diffraction (MAD) experiment. Subsequently, an apo-enzyme structure and a complex between glycogenin and UDP-glucose/Mn2+ were solved by molecular replacement to 1.9 A using the orthorhombic crystal form. Glycogenin contains a conserved DxD motif and an N-terminal beta-alpha-beta Rossmann-like fold that are common to the nucleotide-binding domains of most glycosyltransferases. Although sequence identity amongst glycosyltransferases is minimal, the overall folds are similar. In all of these enzymes, the DxD motif is essential for coordination of the catalytic divalent cation, most commonly Mn2+. We propose a mechanism in which the Mn2+ that associates with the UDP-glucose molecule functions as a Lewis acid to stabilize the leaving group UDP and to facilitate the transfer of the glucose moiety to an intermediate nucleophilic acceptor in the enzyme active site, most likely Asp162. Following transient transfer to Asp162, the glucose moiety is then delivered to the final acceptor, either directly to Tyr194 or to glucose residues already attached to Tyr194. The positioning of the bound UDP-glucose far from Tyr194 in the glycogenin structure raises questions as to the mechanism for the attachment of the first glucose residues. Possibly the initial glucosylation is via inter-dimeric catalysis with an intra-molecular mechanism employed later in oligosaccharide synthesis. |
==About this Structure== | ==About this Structure== | ||
| - | 1LL3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus] with GOL as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Glycogenin_glucosyltransferase Glycogenin glucosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.186 2.4.1.186] Full crystallographic information is available from [http:// | + | 1LL3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus] with <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Glycogenin_glucosyltransferase Glycogenin glucosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.186 2.4.1.186] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LL3 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Oryctolagus cuniculus]] | [[Category: Oryctolagus cuniculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Gibbons, B | + | [[Category: Gibbons, B J.]] |
| - | [[Category: Hurley, T | + | [[Category: Hurley, T D.]] |
| - | [[Category: Roach, P | + | [[Category: Roach, P J.]] |
[[Category: GOL]] | [[Category: GOL]] | ||
[[Category: autocatalytic initiator of glycogen biosynthesis]] | [[Category: autocatalytic initiator of glycogen biosynthesis]] | ||
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[[Category: retaining glycosyltransferase - family 8]] | [[Category: retaining glycosyltransferase - family 8]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:45:56 2008'' |
Revision as of 11:45, 21 February 2008
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Crystal Structure of Rabbit Muscle Glycogenin
Overview
Glycogen is an important storage reserve of glucose present in many organisms, from bacteria to humans. Its biosynthesis is initiated by a specialized protein, glycogenin, which has the unusual property of transferring glucose from UDP-glucose to form an oligosaccharide covalently attached to itself at Tyr194. Glycogen synthase and the branching enzyme complete the synthesis of the polysaccharide. The structure of glycogenin was solved in two different crystal forms. Tetragonal crystals contained a pentamer of dimers in the asymmetric unit arranged in an improper non-crystallographic 10-fold relationship, and orthorhombic crystals contained a monomer in the asymmetric unit that is arranged about a 2-fold crystallographic axis to form a dimer. The structure was first solved to 3.4 A using the tetragonal crystal form and a three-wavelength Se-Met multi-wavelength anomalous diffraction (MAD) experiment. Subsequently, an apo-enzyme structure and a complex between glycogenin and UDP-glucose/Mn2+ were solved by molecular replacement to 1.9 A using the orthorhombic crystal form. Glycogenin contains a conserved DxD motif and an N-terminal beta-alpha-beta Rossmann-like fold that are common to the nucleotide-binding domains of most glycosyltransferases. Although sequence identity amongst glycosyltransferases is minimal, the overall folds are similar. In all of these enzymes, the DxD motif is essential for coordination of the catalytic divalent cation, most commonly Mn2+. We propose a mechanism in which the Mn2+ that associates with the UDP-glucose molecule functions as a Lewis acid to stabilize the leaving group UDP and to facilitate the transfer of the glucose moiety to an intermediate nucleophilic acceptor in the enzyme active site, most likely Asp162. Following transient transfer to Asp162, the glucose moiety is then delivered to the final acceptor, either directly to Tyr194 or to glucose residues already attached to Tyr194. The positioning of the bound UDP-glucose far from Tyr194 in the glycogenin structure raises questions as to the mechanism for the attachment of the first glucose residues. Possibly the initial glucosylation is via inter-dimeric catalysis with an intra-molecular mechanism employed later in oligosaccharide synthesis.
About this Structure
1LL3 is a Single protein structure of sequence from Oryctolagus cuniculus with as ligand. Active as Glycogenin glucosyltransferase, with EC number 2.4.1.186 Full crystallographic information is available from OCA.
Reference
Crystal structure of the autocatalytic initiator of glycogen biosynthesis, glycogenin., Gibbons BJ, Roach PJ, Hurley TD, J Mol Biol. 2002 May 31;319(2):463-77. PMID:12051921
Page seeded by OCA on Thu Feb 21 13:45:56 2008
Categories: Glycogenin glucosyltransferase | Oryctolagus cuniculus | Single protein | Gibbons, B J. | Hurley, T D. | Roach, P J. | GOL | Autocatalytic initiator of glycogen biosynthesis | Beta-alpha-beta rossman-like nucleotide binding fold | Dxd motif | Glycogenin | Non-proline cis peptide bond | Retaining glycosyltransferase - family 8
