Linked Life Data

11714724

Source:http://linkedlifedata.com/resource/pubmed/id/11714724

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2002-2-11
pubmed:databankReference
pubmed:abstractText
Class I alpha1,2-mannosidases (glycosylhydrolase family 47) are key enzymes in the maturation of N-glycans. This protein family includes two distinct enzymatically active subgroups. Subgroup 1 includes the yeast and human endoplasmic reticulum (ER) alpha1,2-mannosidases that primarily trim Man(9)GlcNAc(2) to Man(8)GlcNAc(2) isomer B whereas subgroup 2 includes mammalian Golgi alpha1,2-mannosidases IA, IB, and IC that trim Man(9)GlcNAc(2) to Man(5)GlcNAc(2) via Man(8)GlcNAc(2) isomers A and C. The structure of the catalytic domain of the subgroup 2 alpha1,2-mannosidase from Penicillium citrinum has been determined by molecular replacement at 2.2-A resolution. The fungal alpha1,2-mannosidase is an (alphaalpha)(7)-helix barrel, very similar to the subgroup 1 yeast (Vallée, F., Lipari, F., Yip, P., Sleno, B., Herscovics, A., and Howell, P. L. (2000) EMBO J. 19, 581-588) and human (Vallée, F., Karaveg, K., Herscovics, A., Moremen, K. W., and Howell, P. L. (2000) J. Biol. Chem. 275, 41287-41298) ER enzymes. The location of the conserved acidic residues of the catalytic site and the binding of the inhibitors, kifunensine and 1-deoxymannojirimycin, to the essential calcium ion are conserved in the fungal enzyme. However, there are major structural differences in the oligosaccharide binding site between the two alpha1,2-mannosidase subgroups. In the subgroup 1 enzymes, an arginine residue plays a critical role in stabilizing the oligosaccharide substrate. In the fungal alpha1,2-mannosidase this arginine is replaced by glycine. This replacement and other sequence variations result in a more spacious carbohydrate binding site. Modeling studies of interactions between the yeast, human and fungal enzymes with different Man(8)GlcNAc(2) isomers indicate that there is a greater degree of freedom to bind the oligosaccharide in the active site of the fungal enzyme than in the yeast and human ER alpha1,2-mannosidases.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5620-30
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11714724-1-Deoxynojirimycin, pubmed-meshheading:11714724-Alkaloids, pubmed-meshheading:11714724-Amino Acid Sequence, pubmed-meshheading:11714724-Binding Sites, pubmed-meshheading:11714724-Calcium, pubmed-meshheading:11714724-Catalytic Domain, pubmed-meshheading:11714724-Disulfides, pubmed-meshheading:11714724-Endoplasmic Reticulum, pubmed-meshheading:11714724-Enzyme Inhibitors, pubmed-meshheading:11714724-Golgi Apparatus, pubmed-meshheading:11714724-Humans, pubmed-meshheading:11714724-Mannosidases, pubmed-meshheading:11714724-Models, Molecular, pubmed-meshheading:11714724-Molecular Sequence Data, pubmed-meshheading:11714724-Oligosaccharides, pubmed-meshheading:11714724-Penicillium, pubmed-meshheading:11714724-Protein Binding, pubmed-meshheading:11714724-Protein Conformation, pubmed-meshheading:11714724-Recombinant Proteins, pubmed-meshheading:11714724-Sequence Homology, Amino Acid, pubmed-meshheading:11714724-Stereoisomerism, pubmed-meshheading:11714724-Substrate Specificity
pubmed:year
2002
pubmed:articleTitle
Structure of Penicillium citrinum alpha 1,2-mannosidase reveals the basis for differences in specificity of the endoplasmic reticulum and Golgi class I enzymes.
pubmed:affiliation
Program in Structural Biology and Biochemistry, Research Institute, The Hospital for Sick Children, 555 University Ave., Toronto, Ontario M5G 1X8, Canada.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't