1hty
From Proteopedia
(New page: 200px<br /><applet load="1hty" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hty, resolution 1.40Å" /> '''GOLGI ALPHA-MANNOSID...) |
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| - | [[Image:1hty.gif|left|200px]]<br /><applet load="1hty" size=" | + | [[Image:1hty.gif|left|200px]]<br /><applet load="1hty" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1hty, resolution 1.40Å" /> | caption="1hty, resolution 1.40Å" /> | ||
'''GOLGI ALPHA-MANNOSIDASE II'''<br /> | '''GOLGI ALPHA-MANNOSIDASE II'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Golgi alpha-mannosidase II, a key enzyme in N-glycan processing, is a | + | Golgi alpha-mannosidase II, a key enzyme in N-glycan processing, is a target in the development of anti- cancer therapies. The crystal structure of Drosophila Golgi alpha-mannosidase II in the absence and presence of the anti-cancer agent swainsonine and the inhibitor deoxymannojirimycin reveals a novel protein fold with an active site zinc intricately involved both in the substrate specificity of the enzyme and directly in the catalytic mechanism. Identification of a putative GlcNAc binding pocket in the vicinity of the active site cavity provides a model for the binding of the GlcNAcMan(5)GlcNAc(2) substrate and the consecutive hydrolysis of the alpha1,6- and alpha1,3-linked mannose residues. The enzyme-inhibitor interactions observed provide insight into the catalytic mechanism, opening the door to the design of novel inhibitors of alpha-mannosidase II. |
==About this Structure== | ==About this Structure== | ||
| - | 1HTY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster] with NAG, ZN, TRS and MRD as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Mannosyl-oligosaccharide_1,3-1,6-alpha-mannosidase Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.114 3.2.1.114] Full crystallographic information is available from [http:// | + | 1HTY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=TRS:'>TRS</scene> and <scene name='pdbligand=MRD:'>MRD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Mannosyl-oligosaccharide_1,3-1,6-alpha-mannosidase Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.114 3.2.1.114] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HTY OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase]] | [[Category: Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Elsen, J | + | [[Category: Elsen, J M.H van den.]] |
| - | [[Category: Kuntz, D | + | [[Category: Kuntz, D A.]] |
| - | [[Category: Rose, D | + | [[Category: Rose, D R.]] |
[[Category: MRD]] | [[Category: MRD]] | ||
[[Category: NAG]] | [[Category: NAG]] | ||
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[[Category: three helix bundle]] | [[Category: three helix bundle]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:04:47 2008'' |
Revision as of 11:04, 21 February 2008
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GOLGI ALPHA-MANNOSIDASE II
Overview
Golgi alpha-mannosidase II, a key enzyme in N-glycan processing, is a target in the development of anti- cancer therapies. The crystal structure of Drosophila Golgi alpha-mannosidase II in the absence and presence of the anti-cancer agent swainsonine and the inhibitor deoxymannojirimycin reveals a novel protein fold with an active site zinc intricately involved both in the substrate specificity of the enzyme and directly in the catalytic mechanism. Identification of a putative GlcNAc binding pocket in the vicinity of the active site cavity provides a model for the binding of the GlcNAcMan(5)GlcNAc(2) substrate and the consecutive hydrolysis of the alpha1,6- and alpha1,3-linked mannose residues. The enzyme-inhibitor interactions observed provide insight into the catalytic mechanism, opening the door to the design of novel inhibitors of alpha-mannosidase II.
About this Structure
1HTY is a Single protein structure of sequence from Drosophila melanogaster with , , and as ligands. Active as Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase, with EC number 3.2.1.114 Full crystallographic information is available from OCA.
Reference
Structure of Golgi alpha-mannosidase II: a target for inhibition of growth and metastasis of cancer cells., van den Elsen JM, Kuntz DA, Rose DR, EMBO J. 2001 Jun 15;20(12):3008-17. PMID:11406577
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