Molecular modeling of O6-methylguanine-DNA methyltransferase mutant proteins encoded by single nucleotide polymorphisms

Publication type:
Journal article
Metadata:
Autoren
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000232087900008&DestLinkType=FullRecord&DestApp=WOS_CPL
eISSN
1791-244X
Externe Identifier
  • Clarivate Analytics Document Solution ID: 967JQ
  • PubMed Identifier: 16142386
ISSN
1107-3756
Ausgabe der Veröffentlichung
4
Zeitschrift
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
Schlüsselwörter
  • O-6-methylguanine
  • MGMT
  • molecular modeling
  • single nucleotide polymorphism
Paginierung
553 - 557
Datum der Veröffentlichung
2005
Status
Published
Titel
Molecular modeling of O<SUP>6</SUP>-methylguanine-DNA methyltransferase mutant proteins encoded by single nucleotide polymorphisms
Sub types
  • Article
Ausgabe der Zeitschrift
16

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) acts as a chemoprotectant and mediates resistance to alkylating anti-tumor agents. A number of MGMT single nucleotide polymorphisms (SNPs) have been described. We analyzed by molecular modeling the regions likely to be affected in the MGMT mutant proteins encoded by SNPs. Starting from the crystal structure of non-alkylated MGMT, molecular models of mutant proteins encoded by SNPs have been built. Most of the mutations were found to be located either within the DNA binding region (A121E, A121T, G132R, N123V) or in the vicinity of the active Cys145 (I143V, G160R). A further L84F mutant might affect Zn2+ binding. W65C was found to possibly be unstable.
Addresses
  • Computational Molecular Biophysics, Interdisciplinary Center for Scientific Computing (IWR), University of Heidelberg, Im Neuenheimer Feld 368, 69120 Heidelberg, Germany.
Autoren
eISSN
1791-244X
Externe Identifier
  • PubMed Identifier: 16142386
Open access
false
ISSN
1107-3756
Ausgabe der Veröffentlichung
4
Zeitschrift
International journal of molecular medicine
Schlüsselwörter
  • Humans
  • O(6)-Methylguanine-DNA Methyltransferase
  • Binding Sites
  • Protein Folding
  • Mutation, Missense
  • Polymorphism, Single Nucleotide
  • Algorithms
  • Models, Molecular
Sprache
eng
Medium
Print
Paginierung
553 - 557
Datum der Veröffentlichung
2005
Status
Published
Datum der Datenerfassung
2005
Titel
Molecular modeling of O6-methylguanine-DNA methyltransferase mutant proteins encoded by single nucleotide polymorphisms.
Sub types
  • Comparative Study
  • Journal Article
Ausgabe der Zeitschrift
16

Data source: Europe PubMed Central

Abstract
The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) acts as a chemoprotectant and mediates resistance to alkylating anti-tumor agents. A number of MGMT single nucleotide polymorphisms (SNPs) have been described. We analyzed by molecular modeling the regions likely to be affected in the MGMT mutant proteins encoded by SNPs. Starting from the crystal structure of non-alkylated MGMT, molecular models of mutant proteins encoded by SNPs have been built. Most of the mutations were found to be located either within the DNA binding region (A121E, A121T, G132R, N123V) or in the vicinity of the active Cys145 (I143V, G160R). A further L84F mutant might affect Zn2+ binding. W65C was found to possibly be unstable.
Autoren
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/16142386
ISSN
1107-3756
Ausgabe der Veröffentlichung
4
Zeitschrift
Int J Mol Med
Schlüsselwörter
  • Algorithms
  • Binding Sites
  • Humans
  • Models, Molecular
  • Mutation, Missense
  • O(6)-Methylguanine-DNA Methyltransferase
  • Polymorphism, Single Nucleotide
  • Protein Folding
Sprache
eng
Country
Greece
Paginierung
553 - 557
Datum der Veröffentlichung
2005
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2005
Titel
Molecular modeling of O6-methylguanine-DNA methyltransferase mutant proteins encoded by single nucleotide polymorphisms.
Sub types
  • Comparative Study
  • Journal Article
Ausgabe der Zeitschrift
16

Data source: PubMed

Beziehungen:
Property of

Tools