1on8: Difference between revisions
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[[Image:1on8.jpg|left|200px]]<br /><applet load="1on8" size=" | [[Image:1on8.jpg|left|200px]]<br /><applet load="1on8" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1on8, resolution 2.70Å" /> | caption="1on8, resolution 2.70Å" /> | ||
'''Crystal structure of mouse alpha-1,4-N-acetylhexosaminyltransferase (EXTL2) with UDP and GlcUAb(1-3)Galb(1-O)-naphthalenelmethanol an acceptor substrate analog'''<br /> | '''Crystal structure of mouse alpha-1,4-N-acetylhexosaminyltransferase (EXTL2) with UDP and GlcUAb(1-3)Galb(1-O)-naphthalenelmethanol an acceptor substrate analog'''<br /> | ||
==Overview== | ==Overview== | ||
EXTL2, an alpha1,4-N-acetylhexosaminyltransferase, catalyzes the transfer | EXTL2, an alpha1,4-N-acetylhexosaminyltransferase, catalyzes the transfer reaction of N-acetylglucosamine and N-acetylgalactosamine from the respective UDP-sugars to the non-reducing end of [glucuronic acid]beta1-3[galactose]beta1-O-naphthalenemethanol, an acceptor substrate analog of the natural common linker of various glycosylaminoglycans. We have solved the x-ray crystal structure of the catalytic domain of mouse EXTL2 in the apo-form and with donor substrates UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine. In addition, a structure of the ternary complex with UDP and the acceptor substrate analog [glucuronic acid]beta1-3[galactose]beta1-O-naphthalenemethanol has been determined. These structures reveal three highly conserved residues, Asn-243, Asp-246, and Arg-293, located at the active site. Mutation of these residues greatly decreases the activity. In the ternary complex, an interaction exists between the beta-phosphate of the UDP leaving group and the acceptor hydroxyl of the substrate that may play a functional role in catalysis. These structures represent the first structures from the exostosin gene family and provide important insight into the mechanisms of alpha1,4-N-acetylhexosaminyl transfer in heparan biosynthesis. | ||
==About this Structure== | ==About this Structure== | ||
1ON8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with MN, UDP and EDO as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | 1ON8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=MN:'>MN</scene>, <scene name='pdbligand=UDP:'>UDP</scene> and <scene name='pdbligand=EDO:'>EDO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ON8 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Dong, J.]] | [[Category: Dong, J.]] | ||
[[Category: Kitagawa, H.]] | [[Category: Kitagawa, H.]] | ||
[[Category: Krahn, J | [[Category: Krahn, J M.]] | ||
[[Category: Negishi, M.]] | [[Category: Negishi, M.]] | ||
[[Category: Pedersen, L | [[Category: Pedersen, L C.]] | ||
[[Category: Pedersen, L | [[Category: Pedersen, L G.]] | ||
[[Category: Sugahara, K.]] | [[Category: Sugahara, K.]] | ||
[[Category: Taniguchi, F.]] | [[Category: Taniguchi, F.]] | ||
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[[Category: rossmann fold]] | [[Category: rossmann fold]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:19:30 2008'' | ||
Revision as of 15:19, 21 February 2008
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Crystal structure of mouse alpha-1,4-N-acetylhexosaminyltransferase (EXTL2) with UDP and GlcUAb(1-3)Galb(1-O)-naphthalenelmethanol an acceptor substrate analog
OverviewOverview
EXTL2, an alpha1,4-N-acetylhexosaminyltransferase, catalyzes the transfer reaction of N-acetylglucosamine and N-acetylgalactosamine from the respective UDP-sugars to the non-reducing end of [glucuronic acid]beta1-3[galactose]beta1-O-naphthalenemethanol, an acceptor substrate analog of the natural common linker of various glycosylaminoglycans. We have solved the x-ray crystal structure of the catalytic domain of mouse EXTL2 in the apo-form and with donor substrates UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine. In addition, a structure of the ternary complex with UDP and the acceptor substrate analog [glucuronic acid]beta1-3[galactose]beta1-O-naphthalenemethanol has been determined. These structures reveal three highly conserved residues, Asn-243, Asp-246, and Arg-293, located at the active site. Mutation of these residues greatly decreases the activity. In the ternary complex, an interaction exists between the beta-phosphate of the UDP leaving group and the acceptor hydroxyl of the substrate that may play a functional role in catalysis. These structures represent the first structures from the exostosin gene family and provide important insight into the mechanisms of alpha1,4-N-acetylhexosaminyl transfer in heparan biosynthesis.
About this StructureAbout this Structure
1ON8 is a Single protein structure of sequence from Mus musculus with , and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of an alpha 1,4-N-acetylhexosaminyltransferase (EXTL2), a member of the exostosin gene family involved in heparan sulfate biosynthesis., Pedersen LC, Dong J, Taniguchi F, Kitagawa H, Krahn JM, Pedersen LG, Sugahara K, Negishi M, J Biol Chem. 2003 Apr 18;278(16):14420-8. Epub 2003 Jan 31. PMID:12562774
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