1fo2
From Proteopedia
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'''CRYSTAL STRUCTURE OF HUMAN CLASS I ALPHA1,2-MANNOSIDASE IN COMPLEX WITH 1-DEOXYMANNOJIRIMYCIN''' | '''CRYSTAL STRUCTURE OF HUMAN CLASS I ALPHA1,2-MANNOSIDASE IN COMPLEX WITH 1-DEOXYMANNOJIRIMYCIN''' | ||
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[[Category: Moremen, K W.]] | [[Category: Moremen, K W.]] | ||
[[Category: Vallee, F.]] | [[Category: Vallee, F.]] | ||
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| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 16:33:37 2008'' | |
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Revision as of 13:33, 2 May 2008
CRYSTAL STRUCTURE OF HUMAN CLASS I ALPHA1,2-MANNOSIDASE IN COMPLEX WITH 1-DEOXYMANNOJIRIMYCIN
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
1FO2 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 Page seeded by OCA on Fri May 2 16:33:37 2008
