1wsz
From Proteopedia
(New page: 200px<br /> <applet load="1wsz" size="450" color="white" frame="true" align="right" spinBox="true" caption="1wsz, resolution 1.59Å" /> '''Mutant human ABO(H)...) |
|||
Line 1: | Line 1: | ||
- | [[Image:1wsz.gif|left|200px]]<br /> | + | [[Image:1wsz.gif|left|200px]]<br /><applet load="1wsz" size="350" color="white" frame="true" align="right" spinBox="true" |
- | <applet load="1wsz" size=" | + | |
caption="1wsz, resolution 1.59Å" /> | caption="1wsz, resolution 1.59Å" /> | ||
'''Mutant human ABO(H) blood group transferase A'''<br /> | '''Mutant human ABO(H) blood group transferase A'''<br /> | ||
==Overview== | ==Overview== | ||
- | The human ABO(H) blood group antigens are carbohydrate structures | + | The human ABO(H) blood group antigens are carbohydrate structures generated by glycosyltransferase enzymes. Glycosyltransferase A (GTA) uses UDP-GalNAc as a donor to transfer a monosaccharide residue to Fuc alpha1-2Gal beta-R (H)-terminating acceptors. Similarly, glycosyltransferase B (GTB) catalyzes the transfer of a monosaccharide residue from UDP-Gal to the same acceptors. These are highly homologous enzymes differing in only four of 354 amino acids, Arg/Gly-176, Gly/Ser-235, Leu/Met-266, and Gly/Ala-268. Blood group O usually stems from the expression of truncated inactive forms of GTA or GTB. Recently, an O(2) enzyme was discovered that was a full-length form of GTA with three mutations, P74S, R176G, and G268R. We showed previously that the R176G mutation increased catalytic activity with minor effects on substrate binding. Enzyme kinetics and high resolution structural studies of mutant enzymes based on the O(2) blood group transferase reveal that whereas the P74S mutation in the stem region of the protein does not appear to play a role in enzyme inactivation, the G268R mutation completely blocks the donor GalNAc-binding site leaving the acceptor binding site unaffected. |
==Disease== | ==Disease== | ||
Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
- | 1WSZ 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 HG as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Glycoprotein-fucosylgalactoside_alpha-N-acetylgalactosaminyltransferase Glycoprotein-fucosylgalactoside alpha-N-acetylgalactosaminyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.40 2.4.1.40] Full crystallographic information is available from [http:// | + | 1WSZ 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=HG:'>HG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Glycoprotein-fucosylgalactoside_alpha-N-acetylgalactosaminyltransferase Glycoprotein-fucosylgalactoside alpha-N-acetylgalactosaminyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.40 2.4.1.40] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WSZ OCA]. |
==Reference== | ==Reference== | ||
Line 18: | Line 17: | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
- | [[Category: Barry, C | + | [[Category: Barry, C H.]] |
[[Category: Blancher, A.]] | [[Category: Blancher, A.]] | ||
- | [[Category: Borisova, S | + | [[Category: Borisova, S N.]] |
- | [[Category: Evans, S | + | [[Category: Evans, S V.]] |
- | [[Category: Lee, H | + | [[Category: Lee, H J.]] |
- | [[Category: Palcic, M | + | [[Category: Palcic, M M.]] |
- | [[Category: Seto, N | + | [[Category: Seto, N O.L.]] |
- | [[Category: Zheng, R | + | [[Category: Zheng, R B.]] |
[[Category: HG]] | [[Category: HG]] | ||
[[Category: transferase]] | [[Category: transferase]] | ||
- | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:47:46 2008'' |
Revision as of 13:47, 21 February 2008
|
Mutant human ABO(H) blood group transferase A
Contents |
Overview
The human ABO(H) blood group antigens are carbohydrate structures generated by glycosyltransferase enzymes. Glycosyltransferase A (GTA) uses UDP-GalNAc as a donor to transfer a monosaccharide residue to Fuc alpha1-2Gal beta-R (H)-terminating acceptors. Similarly, glycosyltransferase B (GTB) catalyzes the transfer of a monosaccharide residue from UDP-Gal to the same acceptors. These are highly homologous enzymes differing in only four of 354 amino acids, Arg/Gly-176, Gly/Ser-235, Leu/Met-266, and Gly/Ala-268. Blood group O usually stems from the expression of truncated inactive forms of GTA or GTB. Recently, an O(2) enzyme was discovered that was a full-length form of GTA with three mutations, P74S, R176G, and G268R. We showed previously that the R176G mutation increased catalytic activity with minor effects on substrate binding. Enzyme kinetics and high resolution structural studies of mutant enzymes based on the O(2) blood group transferase reveal that whereas the P74S mutation in the stem region of the protein does not appear to play a role in enzyme inactivation, the G268R mutation completely blocks the donor GalNAc-binding site leaving the acceptor binding site unaffected.
Disease
Known disease associated with this structure: Blood group, ABO system OMIM:[110300]
About this Structure
1WSZ is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Glycoprotein-fucosylgalactoside alpha-N-acetylgalactosaminyltransferase, with EC number 2.4.1.40 Full crystallographic information is available from OCA.
Reference
Structural basis for the inactivity of human blood group O2 glycosyltransferase., Lee HJ, Barry CH, Borisova SN, Seto NO, Zheng RB, Blancher A, Evans SV, Palcic MM, J Biol Chem. 2005 Jan 7;280(1):525-9. Epub 2004 Oct 8. PMID:15475562
Page seeded by OCA on Thu Feb 21 15:47:46 2008