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1fmi

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[[Image:1fmi.gif|left|200px]]
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{{STRUCTURE_1fmi| PDB=1fmi | SCENE= }}
{{STRUCTURE_1fmi| PDB=1fmi | SCENE= }}
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'''CRYSTAL STRUCTURE OF HUMAN CLASS I ALPHA1,2-MANNOSIDASE'''
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===CRYSTAL STRUCTURE OF HUMAN CLASS I ALPHA1,2-MANNOSIDASE===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 10995765 is the PubMed ID number.
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{{ABSTRACT_PUBMED_10995765}}
==About this Structure==
==About this Structure==
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[[Category: Vallee, F.]]
[[Category: Vallee, F.]]
[[Category: Alpha-alpha7 barrel]]
[[Category: Alpha-alpha7 barrel]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 16:30:16 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 03:29:10 2008''

Revision as of 00:29, 1 July 2008

Template:STRUCTURE 1fmi

CRYSTAL STRUCTURE OF HUMAN CLASS I ALPHA1,2-MANNOSIDASE

Template:ABSTRACT PUBMED 10995765

About this Structure

1FMI is a Single protein structure of sequence from Homo sapiens. 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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