1ps3
From Proteopedia
(New page: 200px<br /><applet load="1ps3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ps3, resolution 1.80Å" /> '''Golgi alpha-mannosid...) |
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| - | [[Image:1ps3.jpg|left|200px]]<br /><applet load="1ps3" size=" | + | [[Image:1ps3.jpg|left|200px]]<br /><applet load="1ps3" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1ps3, resolution 1.80Å" /> | caption="1ps3, resolution 1.80Å" /> | ||
'''Golgi alpha-mannosidase II in complex with kifunensine'''<br /> | '''Golgi alpha-mannosidase II in complex with kifunensine'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Mannosidases are key enzymes in the eukaryotic N-glycosylation pathway. | + | Mannosidases are key enzymes in the eukaryotic N-glycosylation pathway. These enzymes fall into two broad classes (I and II) and are characteristically different in catalytic mechanism, sequence, and structure. Kifunensine is an alkaloid that is a strong inhibitor against class I alpha-mannosidases but is only a weak inhibitor against class II alpha-mannosidases. In this paper, the 1.80 A resolution crystal structure of kifunensine bound to Drosophila melanogaster Golgi alpha-mannosidase II (dGMII) is presented. Kifunensine adopts a (1,4)B boat conformation in the class II dGMII, which contrasts the (1)C(4) chair conformation seen in class I human endoplasmic reticulum alpha1,2 mannosidase (hERMI, PDB ). The observed conformations are higher in conformational energy than the global minimum (4)C(1) conformation, although the conformation in hERMI is closer to the minimum, as supported by an energy calculation. Differing conformations of 1-deoxymannojirimycin were also observed: a (4)C(1) and (1)C(4) conformation in dGMII and hERMI, respectively. Thus, these two alpha-mannosidase classes distort these inhibitors in distinct manners. This is likely indicative of the binding characteristics of the two different catalytic mechanisms of these enzymes. |
==About this Structure== | ==About this Structure== | ||
| - | 1PS3 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, KIF 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:// | + | 1PS3 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=KIF:'>KIF</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=1PS3 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: Kuntz, D | + | [[Category: Kuntz, D A.]] |
| - | [[Category: Rose, D | + | [[Category: Rose, D R.]] |
[[Category: Shah, N.]] | [[Category: Shah, N.]] | ||
[[Category: KIF]] | [[Category: KIF]] | ||
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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 14:31:56 2008'' |
Revision as of 12:31, 21 February 2008
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Golgi alpha-mannosidase II in complex with kifunensine
Overview
Mannosidases are key enzymes in the eukaryotic N-glycosylation pathway. These enzymes fall into two broad classes (I and II) and are characteristically different in catalytic mechanism, sequence, and structure. Kifunensine is an alkaloid that is a strong inhibitor against class I alpha-mannosidases but is only a weak inhibitor against class II alpha-mannosidases. In this paper, the 1.80 A resolution crystal structure of kifunensine bound to Drosophila melanogaster Golgi alpha-mannosidase II (dGMII) is presented. Kifunensine adopts a (1,4)B boat conformation in the class II dGMII, which contrasts the (1)C(4) chair conformation seen in class I human endoplasmic reticulum alpha1,2 mannosidase (hERMI, PDB ). The observed conformations are higher in conformational energy than the global minimum (4)C(1) conformation, although the conformation in hERMI is closer to the minimum, as supported by an energy calculation. Differing conformations of 1-deoxymannojirimycin were also observed: a (4)C(1) and (1)C(4) conformation in dGMII and hERMI, respectively. Thus, these two alpha-mannosidase classes distort these inhibitors in distinct manners. This is likely indicative of the binding characteristics of the two different catalytic mechanisms of these enzymes.
About this Structure
1PS3 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
Comparison of kifunensine and 1-deoxymannojirimycin binding to class I and II alpha-mannosidases demonstrates different saccharide distortions in inverting and retaining catalytic mechanisms., Shah N, Kuntz DA, Rose DR, Biochemistry. 2003 Dec 2;42(47):13812-6. PMID:14636047
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