Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
The kinetic analysis of recognition of the damaged nucleotides by mutant forms of the 8-oxoguanine DNA glycosylase hOGG1. / Lukina, M. V.; Kuznetsova, A. A.; Kuznetsov, N. A. и др.
в: Russian Journal of Bioorganic Chemistry, Том 43, № 1, 01.01.2017, стр. 1-12.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - The kinetic analysis of recognition of the damaged nucleotides by mutant forms of the 8-oxoguanine DNA glycosylase hOGG1
AU - Lukina, M. V.
AU - Kuznetsova, A. A.
AU - Kuznetsov, N. A.
AU - Fedorova, O. S.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - We have investigated the role of Tyr-203, His-270, and Lys-249 amino acid residues from the 8-oxoguanine glycosylase (hOGG1) active site in the process of recognition of 7,8-dihydro-8-oxoguanine (oxoG) damaged nucleotide and in the catalytic stages of enzymatic reaction. The pre-steady state kinetic analysis of conformational transitions of mutant forms of the enzyme and model DNA substrates during the enzymatic process revealed that the studied amino acid residues are involved in the specific binding of DNA substrates. The Tyr-203 is responsible for recognition of the damaged nucleotide; interaction between His-270 and DNA is necessary for the formation of the catalytically active complex with the oxoG-containing DNA. The Lys-249 acts not only as one of the catalytically important amino acids of the active site of the enzyme, but also plays a significant role in the formation of specific enzyme–substrate complex. The present study significantly complements the molecular-kinetic model of the enzymatic reaction and helps to clarify the origin of the high specificity of hOGG1 to oxidized bases in DNA.
AB - We have investigated the role of Tyr-203, His-270, and Lys-249 amino acid residues from the 8-oxoguanine glycosylase (hOGG1) active site in the process of recognition of 7,8-dihydro-8-oxoguanine (oxoG) damaged nucleotide and in the catalytic stages of enzymatic reaction. The pre-steady state kinetic analysis of conformational transitions of mutant forms of the enzyme and model DNA substrates during the enzymatic process revealed that the studied amino acid residues are involved in the specific binding of DNA substrates. The Tyr-203 is responsible for recognition of the damaged nucleotide; interaction between His-270 and DNA is necessary for the formation of the catalytically active complex with the oxoG-containing DNA. The Lys-249 acts not only as one of the catalytically important amino acids of the active site of the enzyme, but also plays a significant role in the formation of specific enzyme–substrate complex. The present study significantly complements the molecular-kinetic model of the enzymatic reaction and helps to clarify the origin of the high specificity of hOGG1 to oxidized bases in DNA.
KW - conformational changes
KW - human 8-oxoguanine DNA glycosylase
KW - mechanism of recognition
KW - pre-steady state kinetics
KW - specificity
KW - SPECIFICITY
KW - STEADY-STATE KINETICS
KW - ACTIVE-SITE
KW - REPAIR ENZYME
KW - CONFORMATIONAL DYNAMICS
KW - SACCHAROMYCES-CEREVISIAE
KW - SUBSTRATE RECOGNITION
KW - FLUORESCENCE
KW - OGG1 PROTEIN
KW - LESION RECOGNITION
UR - http://www.scopus.com/inward/record.url?scp=85012927446&partnerID=8YFLogxK
U2 - 10.1134/S1068162017010058
DO - 10.1134/S1068162017010058
M3 - Article
AN - SCOPUS:85012927446
VL - 43
SP - 1
EP - 12
JO - Russian Journal of Bioorganic Chemistry
JF - Russian Journal of Bioorganic Chemistry
SN - 1068-1620
IS - 1
ER -
ID: 8681385