1fo2: Difference between revisions

Revision as of 16:33, 2 May 2008

CRYSTAL STRUCTURE OF HUMAN CLASS I ALPHA1,2-MANNOSIDASE IN COMPLEX WITH 1-DEOXYMANNOJIRIMYCIN

OverviewOverview

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 StructureAbout this Structure

1FO2 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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 [[Image:1fo2.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 1fo2 |SIZE=350|CAPTION= <scene name='initialview01'>1fo2</scene>, resolution 2.38&Aring;
+The line below this paragraph, containing "STRUCTURE_1fo2", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DMJ:1-DEOXYMANNOJIRIMYCIN'>DMJ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Alpha-mannosidase Alpha-mannosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.24 3.2.1.24] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1fo2|  PDB=1fo2  |  SCENE=  }}
-|RELATEDENTRY=[[1fmi|1FMI]], [[1fo3|1FO3]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1fo2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fo2 OCA], [http://www.ebi.ac.uk/pdbsum/1fo2 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1fo2 RCSB]</span>
-}}
 '''CRYSTAL STRUCTURE OF HUMAN CLASS I ALPHA1,2-MANNOSIDASE IN COMPLEX WITH 1-DEOXYMANNOJIRIMYCIN'''
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 [[Category: Moremen, K W.]]
 [[Category: Vallee, F.]]
-[[Category: alpha-alpha7 barrel]]
+[[Category: Alpha-alpha7 barrel]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 16:33:37 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:26:47 2008''