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2ah9
From Proteopedia
(New page: 200px<br /> <applet load="2ah9" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ah9, resolution 2.00Å" /> '''Crystal Structure o...) |
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| - | [[Image:2ah9.gif|left|200px]]<br /> | + | [[Image:2ah9.gif|left|200px]]<br /><applet load="2ah9" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2ah9" size=" | + | |
caption="2ah9, resolution 2.00Å" /> | caption="2ah9, resolution 2.00Å" /> | ||
'''Crystal Structure of Human M340H-Beta-1,4-Galactosyltransferase-I (M340H-B4Gal-T1) in Complex with Chitotriose'''<br /> | '''Crystal Structure of Human M340H-Beta-1,4-Galactosyltransferase-I (M340H-B4Gal-T1) in Complex with Chitotriose'''<br /> | ||
==Overview== | ==Overview== | ||
| - | beta-1,4-Galactosyltransferase-I (beta4Gal-T1) transfers galactose from | + | beta-1,4-Galactosyltransferase-I (beta4Gal-T1) transfers galactose from UDP-galactose to N-acetylglucosamine (GlcNAc) residues of the branched N-linked oligosaccharide chains of glycoproteins. In an N-linked biantennary oligosaccharide chain, one antenna is attached to the 3-hydroxyl-(1,3-arm), and the other to the 6-hydroxyl-(1,6-arm) group of mannose, which is beta-1,4-linked to an N-linked chitobiose, attached to the aspargine residue of a protein. For a better understanding of the branch specificity of beta4Gal-T1 towards the GlcNAc residues of N-glycans, we have carried out kinetic and crystallographic studies with the wild-type human beta4Gal-T1 (h-beta4Gal-T1) and the mutant Met340His-beta4Gal-T1 (h-M340H-beta4Gal-T1) in complex with a GlcNAc-containing pentasaccharide and several GlcNAc-containing trisaccharides present in N-glycans. The oligosaccharides used were: pentasaccharide GlcNAcbeta1,2-Manalpha1,6 (GlcNAcbeta1,2-Manalpha1,3)Man; the 1,6-arm trisaccharide, GlcNAcbeta1,2-Manalpha1,6-Manbeta-OR (1,2-1,6-arm); the 1,3-arm trisaccharides, GlcNAcbeta1,2-Manalpha1,3-Manbeta-OR (1,2-1,3-arm) and GlcNAcbeta1,4-Manalpha1,3-Manbeta-OR (1,4-1,3-arm); and the trisaccharide GlcNAcbeta1,4-GlcNAcbeta1,4-GlcNAc (chitotriose). With the wild-type h-beta4Gal-T1, the K(m) of 1,2-1,6-arm is approximately tenfold lower than for 1,2-1,3-arm and 1,4-1,3-arm, and 22-fold lower than for chitotriose. Crystal structures of h-M340H-beta4Gal-T1 in complex with the pentasaccharide and various trisaccharides at 1.9-2.0A resolution showed that beta4Gal-T1 is in a closed conformation with the oligosaccharide bound to the enzyme, and the 1,2-1,6-arm trisaccharide makes the maximum number of interactions with the enzyme, which is in concurrence with the lowest K(m) for the trisaccharide. Present studies suggest that beta4Gal-T1 interacts preferentially with the 1,2-1,6-arm trisaccharide rather than with the 1,2-1,3-arm or 1,4-1,3-arm of a bi- or tri-antennary oligosaccharide chain of N-glycan. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2AH9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CTO, MN, SO4, UDH, DIO, MES and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/N-acetyllactosamine_synthase N-acetyllactosamine synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.90 2.4.1.90] Full crystallographic information is available from [http:// | + | 2AH9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CTO:'>CTO</scene>, <scene name='pdbligand=MN:'>MN</scene>, <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=UDH:'>UDH</scene>, <scene name='pdbligand=DIO:'>DIO</scene>, <scene name='pdbligand=MES:'>MES</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/N-acetyllactosamine_synthase N-acetyllactosamine synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.90 2.4.1.90] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AH9 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Boeggeman, E.]] | [[Category: Boeggeman, E.]] | ||
| - | [[Category: Qasba, P | + | [[Category: Qasba, P K.]] |
[[Category: Ramakrishnan, B.]] | [[Category: Ramakrishnan, B.]] | ||
[[Category: Ramasamy, V.]] | [[Category: Ramasamy, V.]] | ||
| - | [[Category: Ratner, D | + | [[Category: Ratner, D M.]] |
| - | [[Category: Seeberger, P | + | [[Category: Seeberger, P H.]] |
[[Category: CTO]] | [[Category: CTO]] | ||
[[Category: DIO]] | [[Category: DIO]] | ||
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[[Category: beta1]] | [[Category: beta1]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:27:21 2008'' |
Revision as of 14:27, 21 February 2008
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Crystal Structure of Human M340H-Beta-1,4-Galactosyltransferase-I (M340H-B4Gal-T1) in Complex with Chitotriose
Contents |
Overview
beta-1,4-Galactosyltransferase-I (beta4Gal-T1) transfers galactose from UDP-galactose to N-acetylglucosamine (GlcNAc) residues of the branched N-linked oligosaccharide chains of glycoproteins. In an N-linked biantennary oligosaccharide chain, one antenna is attached to the 3-hydroxyl-(1,3-arm), and the other to the 6-hydroxyl-(1,6-arm) group of mannose, which is beta-1,4-linked to an N-linked chitobiose, attached to the aspargine residue of a protein. For a better understanding of the branch specificity of beta4Gal-T1 towards the GlcNAc residues of N-glycans, we have carried out kinetic and crystallographic studies with the wild-type human beta4Gal-T1 (h-beta4Gal-T1) and the mutant Met340His-beta4Gal-T1 (h-M340H-beta4Gal-T1) in complex with a GlcNAc-containing pentasaccharide and several GlcNAc-containing trisaccharides present in N-glycans. The oligosaccharides used were: pentasaccharide GlcNAcbeta1,2-Manalpha1,6 (GlcNAcbeta1,2-Manalpha1,3)Man; the 1,6-arm trisaccharide, GlcNAcbeta1,2-Manalpha1,6-Manbeta-OR (1,2-1,6-arm); the 1,3-arm trisaccharides, GlcNAcbeta1,2-Manalpha1,3-Manbeta-OR (1,2-1,3-arm) and GlcNAcbeta1,4-Manalpha1,3-Manbeta-OR (1,4-1,3-arm); and the trisaccharide GlcNAcbeta1,4-GlcNAcbeta1,4-GlcNAc (chitotriose). With the wild-type h-beta4Gal-T1, the K(m) of 1,2-1,6-arm is approximately tenfold lower than for 1,2-1,3-arm and 1,4-1,3-arm, and 22-fold lower than for chitotriose. Crystal structures of h-M340H-beta4Gal-T1 in complex with the pentasaccharide and various trisaccharides at 1.9-2.0A resolution showed that beta4Gal-T1 is in a closed conformation with the oligosaccharide bound to the enzyme, and the 1,2-1,6-arm trisaccharide makes the maximum number of interactions with the enzyme, which is in concurrence with the lowest K(m) for the trisaccharide. Present studies suggest that beta4Gal-T1 interacts preferentially with the 1,2-1,6-arm trisaccharide rather than with the 1,2-1,3-arm or 1,4-1,3-arm of a bi- or tri-antennary oligosaccharide chain of N-glycan.
Disease
Known diseases associated with this structure: Congenital disorder of glycosylation, type IId OMIM:[137060]
About this Structure
2AH9 is a Single protein structure of sequence from Homo sapiens with , , , , , and as ligands. Active as N-acetyllactosamine synthase, with EC number 2.4.1.90 Full crystallographic information is available from OCA.
Reference
Oligosaccharide preferences of beta1,4-galactosyltransferase-I: crystal structures of Met340His mutant of human beta1,4-galactosyltransferase-I with a pentasaccharide and trisaccharides of the N-glycan moiety., Ramasamy V, Ramakrishnan B, Boeggeman E, Ratner DM, Seeberger PH, Qasba PK, J Mol Biol. 2005 Oct 14;353(1):53-67. PMID:16157350
Page seeded by OCA on Thu Feb 21 16:27:21 2008
Categories: Homo sapiens | N-acetyllactosamine synthase | Single protein | Boeggeman, E. | Qasba, P K. | Ramakrishnan, B. | Ramasamy, V. | Ratner, D M. | Seeberger, P H. | CTO | DIO | GOL | MES | MN | SO4 | UDH | 4-galactosyltransferase-i; trisaccharide; chitotriose; closed conformation; mutant | Beta1
