2d7r
From Proteopedia
(New page: 200px<br /> <applet load="2d7r" size="450" color="white" frame="true" align="right" spinBox="true" caption="2d7r, resolution 2.8Å" /> '''Crystal structure of...) |
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| - | [[Image:2d7r.gif|left|200px]]<br /> | + | [[Image:2d7r.gif|left|200px]]<br /><applet load="2d7r" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="2d7r, resolution 2.8Å" /> | caption="2d7r, resolution 2.8Å" /> | ||
'''Crystal structure of pp-GalNAc-T10 complexed with GalNAc-Ser on lectin domain'''<br /> | '''Crystal structure of pp-GalNAc-T10 complexed with GalNAc-Ser on lectin domain'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Mucin-type O-glycans are important carbohydrate chains involved in | + | Mucin-type O-glycans are important carbohydrate chains involved in differentiation and malignant transformation. Biosynthesis of the O-glycan is initiated by the transfer of N-acetylgalactosamine (GalNAc) which is catalyzed by UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferases (pp-GalNAc-Ts). Here we present crystal structures of the pp-GalNAc-T10 isozyme, which has specificity for glycosylated peptides, in complex with the hydrolyzed donor substrate UDP-GalNAc and in complex with GalNAc-serine. A structural comparison with uncomplexed pp-GalNAc-T1 suggests that substantial conformational changes occur in two loops near the catalytic center upon donor substrate binding, and that a distinct interdomain arrangement between the catalytic and lectin domains forms a narrow cleft for acceptor substrates. The distance between the catalytic center and the carbohydrate-binding site on the lectin beta sub-domain influences the position of GalNAc glycosylation on GalNAc-glycosylated peptide substrates. A chimeric enzyme in which the two domains of pp-GalNAc-T10 are connected by a linker from pp-GalNAc-T1 acquires activity toward non-glycosylated acceptors, identifying a potential mechanism for generating the various acceptor specificities in different isozymes to produce a wide range of O-glycans. |
==About this Structure== | ==About this Structure== | ||
| - | 2D7R 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 NAG, NGA, MN, TNR and UDP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Polypeptide_N-acetylgalactosaminyltransferase Polypeptide N-acetylgalactosaminyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.41 2.4.1.41] Full crystallographic information is available from [http:// | + | 2D7R 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=NAG:'>NAG</scene>, <scene name='pdbligand=NGA:'>NGA</scene>, <scene name='pdbligand=MN:'>MN</scene>, <scene name='pdbligand=TNR:'>TNR</scene> and <scene name='pdbligand=UDP:'>UDP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Polypeptide_N-acetylgalactosaminyltransferase Polypeptide N-acetylgalactosaminyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.41 2.4.1.41] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2D7R OCA]. |
==Reference== | ==Reference== | ||
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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 16:55:58 2008'' |
Revision as of 14:55, 21 February 2008
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Crystal structure of pp-GalNAc-T10 complexed with GalNAc-Ser on lectin domain
Overview
Mucin-type O-glycans are important carbohydrate chains involved in differentiation and malignant transformation. Biosynthesis of the O-glycan is initiated by the transfer of N-acetylgalactosamine (GalNAc) which is catalyzed by UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferases (pp-GalNAc-Ts). Here we present crystal structures of the pp-GalNAc-T10 isozyme, which has specificity for glycosylated peptides, in complex with the hydrolyzed donor substrate UDP-GalNAc and in complex with GalNAc-serine. A structural comparison with uncomplexed pp-GalNAc-T1 suggests that substantial conformational changes occur in two loops near the catalytic center upon donor substrate binding, and that a distinct interdomain arrangement between the catalytic and lectin domains forms a narrow cleft for acceptor substrates. The distance between the catalytic center and the carbohydrate-binding site on the lectin beta sub-domain influences the position of GalNAc glycosylation on GalNAc-glycosylated peptide substrates. A chimeric enzyme in which the two domains of pp-GalNAc-T10 are connected by a linker from pp-GalNAc-T1 acquires activity toward non-glycosylated acceptors, identifying a potential mechanism for generating the various acceptor specificities in different isozymes to produce a wide range of O-glycans.
About this Structure
2D7R is a Single protein structure of sequence from Homo sapiens with , , , and as ligands. Active as Polypeptide N-acetylgalactosaminyltransferase, with EC number 2.4.1.41 Full crystallographic information is available from OCA.
Reference
Structural basis of carbohydrate transfer activity by human UDP-GalNAc: polypeptide alpha-N-acetylgalactosaminyltransferase (pp-GalNAc-T10)., Kubota T, Shiba T, Sugioka S, Furukawa S, Sawaki H, Kato R, Wakatsuki S, Narimatsu H, J Mol Biol. 2006 Jun 9;359(3):708-27. Epub 2006 Apr 19. PMID:16650853
Page seeded by OCA on Thu Feb 21 16:55:58 2008
Categories: Homo sapiens | Polypeptide N-acetylgalactosaminyltransferase | Single protein | Kato, R. | Kubota, T. | Narimatsu, H. | Shiba, T. | Sugioka, S. | Wakatsuki, S. | MN | NAG | NGA | TNR | UDP | Beta trefoil | Rossmann fold
