1fmi
From Proteopedia
(New page: 200px<br /> <applet load="1fmi" size="450" color="white" frame="true" align="right" spinBox="true" caption="1fmi, resolution 1.90Å" /> '''CRYSTAL STRUCTURE O...) |
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| - | [[Image:1fmi.gif|left|200px]]<br /> | + | [[Image:1fmi.gif|left|200px]]<br /><applet load="1fmi" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1fmi" size=" | + | |
caption="1fmi, resolution 1.90Å" /> | caption="1fmi, resolution 1.90Å" /> | ||
'''CRYSTAL STRUCTURE OF HUMAN CLASS I ALPHA1,2-MANNOSIDASE'''<br /> | '''CRYSTAL STRUCTURE OF HUMAN CLASS I ALPHA1,2-MANNOSIDASE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Endoplasmic reticulum (ER) class I alpha1,2-mannosidase (also known as ER | + | Endoplasmic reticulum (ER) class I alpha1,2-mannosidase (also known as ER alpha-mannosidase I) is a critical enzyme in the maturation of N-linked oligosaccharides and ER-associated degradation. Trimming of a single mannose residue acts as a signal to target misfolded glycoproteins for degradation by the proteasome. Crystal structures of the catalytic domain of human ER class I alpha1,2-mannosidase have been determined both in the presence and absence of the potent inhibitors kifunensine and 1-deoxymannojirimycin. Both inhibitors bind to the protein at the bottom of the active-site cavity, with the essential calcium ion coordinating the O-2' and O-3' hydroxyls and stabilizing the six-membered rings of both inhibitors in a (1)C(4) conformation. This is the first direct evidence of the role of the calcium ion. The lack of major conformational changes upon inhibitor binding and structural comparisons with the yeast alpha1, 2-mannosidase enzyme-product complex suggest that this class of inverting enzymes has a novel catalytic mechanism. The structures also provide insight into the specificity of this class of enzymes and provide a blueprint for the future design of novel inhibitors that prevent degradation of misfolded proteins in genetic diseases. |
==About this Structure== | ==About this Structure== | ||
| - | 1FMI 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 CA and SO4 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Mannosyl-oligosaccharide_1,2-alpha-mannosidase Mannosyl-oligosaccharide 1,2-alpha-mannosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.113 3.2.1.113] Full crystallographic information is available from [http:// | + | 1FMI 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=CA:'>CA</scene> and <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Mannosyl-oligosaccharide_1,2-alpha-mannosidase Mannosyl-oligosaccharide 1,2-alpha-mannosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.113 3.2.1.113] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FMI OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Herscovics, A.]] | [[Category: Herscovics, A.]] | ||
| - | [[Category: Howell, P | + | [[Category: Howell, P L.]] |
[[Category: Karaveg, K.]] | [[Category: Karaveg, K.]] | ||
| - | [[Category: Moremen, K | + | [[Category: Moremen, K W.]] |
[[Category: Vallee, F.]] | [[Category: Vallee, F.]] | ||
[[Category: CA]] | [[Category: CA]] | ||
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[[Category: alpha-alpha7 barrel]] | [[Category: alpha-alpha7 barrel]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:40:15 2008'' |
Revision as of 10:40, 21 February 2008
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CRYSTAL STRUCTURE OF HUMAN CLASS I ALPHA1,2-MANNOSIDASE
Overview
Endoplasmic reticulum (ER) class I alpha1,2-mannosidase (also known as ER alpha-mannosidase I) is a critical enzyme in the maturation of N-linked oligosaccharides and ER-associated degradation. Trimming of a single mannose residue acts as a signal to target misfolded glycoproteins for degradation by the proteasome. Crystal structures of the catalytic domain of human ER class I alpha1,2-mannosidase have been determined both in the presence and absence of the potent inhibitors kifunensine and 1-deoxymannojirimycin. Both inhibitors bind to the protein at the bottom of the active-site cavity, with the essential calcium ion coordinating the O-2' and O-3' hydroxyls and stabilizing the six-membered rings of both inhibitors in a (1)C(4) conformation. This is the first direct evidence of the role of the calcium ion. The lack of major conformational changes upon inhibitor binding and structural comparisons with the yeast alpha1, 2-mannosidase enzyme-product complex suggest that this class of inverting enzymes has a novel catalytic mechanism. The structures also provide insight into the specificity of this class of enzymes and provide a blueprint for the future design of novel inhibitors that prevent degradation of misfolded proteins in genetic diseases.
About this Structure
1FMI is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Mannosyl-oligosaccharide 1,2-alpha-mannosidase, with EC number 3.2.1.113 Full crystallographic information is available from OCA.
Reference
Structural basis for catalysis and inhibition of N-glycan processing class I alpha 1,2-mannosidases., Vallee F, Karaveg K, Herscovics A, Moremen KW, Howell PL, J Biol Chem. 2000 Dec 29;275(52):41287-98. PMID:10995765
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