Linked Life Data

20713123

Source:http://linkedlifedata.com/resource/pubmed/id/20713123

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2010-12-6
pubmed:abstractText
The sensitivity to denaturant stress of the major (AGT-Ma) and the minor (AGT-Mi) allele of alanine:glyoxylate aminotransferase and P11L mutant has been examined by studying their urea-induced equilibrium unfolding processes with various spectroscopic and analytical techniques. AGT-Ma loses pyridoxal 5'-phosphate (PLP) and unfolds completely without exposing significant hydrophobic clusters through a two-state model (C(m) ? 6.9 M urea). Instead, the unfolding of AGT-Mi and P11L variant proceeds in two steps. The first transition (C(m) ? 4.6 M urea) involves PLP release, dimer dissociation and exposure of hydrophobic patches leading to a self-associated intermediate which is converted to an unfolded monomer in the second step. The unfolding pathways of apoAGT-Mi and apoP11L are similar to each other, but different from that of apoAGT-Ma. Notably, the monomerization step in apoAGT-Mi and apoP11L occurs with a C(m) value (?1.6 M urea) lower than in apoAGT-Ma (?2.4 M urea). These data indicate that Pro11 is relevant for the stability of both the dimeric structure and the PLP binding site of AGT. Moreover, to understand the pathogenic consequences of G170R mutation on AGT-Mi at the protein level, G170R-Mi has been characterized. HoloG170R-Mi exhibits spectroscopic and catalytic features and urea unfolding profiles comparable to those of AGT-Mi, while the apo form monomerizes with a C(m) of ?1.1 M urea. These biochemical results are discussed in the light of the characteristics of the enzymatic phenotype of PH1 patients bearing G170R mutation in AGT-Mi and the positive response of these patients to pyridoxine treatment.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1638-6183
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Masson SAS. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
92
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1801-11
pubmed:meshHeading
pubmed-meshheading:20713123-Alleles, pubmed-meshheading:20713123-Amino Acid Substitution, pubmed-meshheading:20713123-Binding, Competitive, pubmed-meshheading:20713123-Biocatalysis, pubmed-meshheading:20713123-Circular Dichroism, pubmed-meshheading:20713123-Enzyme Stability, pubmed-meshheading:20713123-Humans, pubmed-meshheading:20713123-Isoenzymes, pubmed-meshheading:20713123-Kinetics, pubmed-meshheading:20713123-Liver, pubmed-meshheading:20713123-Models, Molecular, pubmed-meshheading:20713123-Mutation, pubmed-meshheading:20713123-Peroxisomes, pubmed-meshheading:20713123-Protein Binding, pubmed-meshheading:20713123-Protein Denaturation, pubmed-meshheading:20713123-Protein Structure, Secondary, pubmed-meshheading:20713123-Protein Structure, Tertiary, pubmed-meshheading:20713123-Protein Unfolding, pubmed-meshheading:20713123-Pyridoxal Phosphate, pubmed-meshheading:20713123-Spectrometry, Fluorescence, pubmed-meshheading:20713123-Transaminases, pubmed-meshheading:20713123-Urea
pubmed:year
2010
pubmed:articleTitle
Human liver peroxisomal alanine:glyoxylate aminotransferase: Different stability under chemical stress of the major allele, the minor allele, and its pathogenic G170R variant.
pubmed:affiliation
Dipartimento di Scienze della Vita e della Riproduzione, Sezione di Chimica Biologica, Facoltà di Medicina e Chirurgia, Università degli Studi di Verona, Strada Le Grazie, 8 37134 Verona, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't