Linked Life Data

11419947

Source:http://linkedlifedata.com/resource/pubmed/id/11419947

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-6-22
pubmed:databankReference
pubmed:abstractText
The lactose synthase (LS) enzyme is a 1:1 complex of a catalytic component, beta1,4-galactosyltransferse (beta4Gal-T1) and a regulatory component, alpha-lactalbumin (LA), a mammary gland-specific protein. LA promotes the binding of glucose (Glc) to beta4Gal-T1, thereby altering its sugar acceptor specificity from N-acetylglucosamine (GlcNAc) to glucose, which enables LS to synthesize lactose, the major carbohydrate component of milk. The crystal structures of LS bound with various substrates were solved at 2 A resolution. These structures reveal that upon substrate binding to beta4Gal-T1, a large conformational change occurs in the region comprising residues 345 to 365. This repositions His347 in such a way that it can participate in the coordination of a metal ion, and creates a sugar and LA-binding site. At the sugar-acceptor binding site, a hydrophobic N-acetyl group-binding pocket is found, formed by residues Arg359, Phe360 and Ile363. In the Glc-bound structure, this hydrophobic pocket is absent. For the binding of Glc to LS, a reorientation of the Arg359 side-chain occurs, which blocks the hydrophobic pocket and maximizes the interactions with the Glc molecule. Thus, the role of LA is to hold Glc by hydrogen bonding with the O-1 hydroxyl group in the acceptor-binding site on beta4Gal-T1, while the N-acetyl group-binding pocket in beta4Gal-T1 adjusts to maximize the interactions with the Glc molecule. This study provides details of a structural basis for the partially ordered kinetic mechanism proposed for lactose synthase.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-2836
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Academic Press.
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
310
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
205-18
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11419947-Acetylglucosamine, pubmed-meshheading:11419947-Animals, pubmed-meshheading:11419947-Binding Sites, pubmed-meshheading:11419947-Catalysis, pubmed-meshheading:11419947-Catalytic Domain, pubmed-meshheading:11419947-Cattle, pubmed-meshheading:11419947-Crystallography, X-Ray, pubmed-meshheading:11419947-Galactosyltransferases, pubmed-meshheading:11419947-Glucose, pubmed-meshheading:11419947-Hydrogen Bonding, pubmed-meshheading:11419947-Kinetics, pubmed-meshheading:11419947-Lactalbumin, pubmed-meshheading:11419947-Lactose Synthase, pubmed-meshheading:11419947-Manganese, pubmed-meshheading:11419947-Mice, pubmed-meshheading:11419947-Models, Molecular, pubmed-meshheading:11419947-Protein Binding, pubmed-meshheading:11419947-Protein Conformation, pubmed-meshheading:11419947-Substrate Specificity, pubmed-meshheading:11419947-Uridine Diphosphate Galactose
pubmed:year
2001
pubmed:articleTitle
Crystal structure of lactose synthase reveals a large conformational change in its catalytic component, the beta1,4-galactosyltransferase-I.
pubmed:affiliation
Structural Glycobiology Section, Intramural Research Support Program-SAIC, Laboratory of Experimental and Computational Biology, CCR, NCI, Frederick, MD 21702, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.