1hww: Difference between revisions

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[[Image:1hww.gif|left|200px]]<br /><applet load="1hww" size="350" color="white" frame="true" align="right" spinBox="true"
[[Image:1hww.gif|left|200px]]
caption="1hww, resolution 1.87&Aring;" />
 
'''GOLGI ALPHA-MANNOSIDASE II IN COMPLEX WITH SWAINSONINE'''<br />
{{Structure
|PDB= 1hww |SIZE=350|CAPTION= <scene name='initialview01'>1hww</scene>, resolution 1.87&Aring;
|SITE=
|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=SWA:1S-8AB-OCTAHYDRO-INDOLIZIDINE-1A,2A,8B-TRIOL'>SWA</scene> and <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene>
|ACTIVITY= [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]
|GENE=
}}
 
'''GOLGI ALPHA-MANNOSIDASE II IN COMPLEX WITH SWAINSONINE'''
 


==Overview==
==Overview==
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==About this Structure==
==About this Structure==
1HWW 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=SWA:'>SWA</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=1HWW OCA].  
1HWW is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HWW OCA].  


==Reference==
==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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11406577 11406577]
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:[http://www.ncbi.nlm.nih.gov/pubmed/11406577 11406577]
[[Category: Drosophila melanogaster]]
[[Category: Drosophila melanogaster]]
[[Category: Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase]]
[[Category: Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase]]
Line 21: Line 30:
[[Category: SWA]]
[[Category: SWA]]
[[Category: ZN]]
[[Category: ZN]]
[[Category: 2 c-terminal beta barrels]]
[[Category: 2 c-terminal beta barrel]]
[[Category: n-terminal alpha-beta domain]]
[[Category: n-terminal alpha-beta domain]]
[[Category: three helix bundle]]
[[Category: three helix bundle]]


''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:05:35 2008''
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:42:32 2008''

Revision as of 09:42, 20 March 2008

File:1hww.gif


Drag the structure with the mouse to rotate
1hww, resolution 1.87Å
Ligands: NAG, ZN, SWA and MRD
Activity: Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase, with EC number 3.2.1.114
Coordinates: save as pdb, mmCIF, xml



GOLGI ALPHA-MANNOSIDASE II IN COMPLEX WITH SWAINSONINE


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

1HWW is a Single protein structure of sequence from Drosophila melanogaster. 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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