O6 methylguanine DNA methyltransferase

O6 methylguanine DNA methyltransferase
	Ribbon / surface model of MGMT on O6-methylguanyl-DNA according to PDB 1T38 . The outwardly turned methylguanine is shown as a dome.
	Existing structural data : 1eh6 , 1eh7 , 1eh8 , 1qnt , 1t38 , 1t39 , 1yfh
Properties of human protein
Mass / length primary structure	207 amino acids
Cofactor	zinc
Identifier
Gene names	MGMT ; AGT
External IDs	OMIM : 156569 ; UniProt : P16455 ; MGI : 96977 ;
Enzyme classification
EC, category	2.1.1.63 , methyltransferase
Response type	(De) methylation
Substrate	DNA with O6-methylguanine + protein with cysteine
Products	DNA with guanine + protein with S-methylcysteine
Occurrence
Homology family	MGMT
Parent taxon	Creature

O6-methylguanine-DNA-methyltransferase (MGMT) (also 6-O-methylguanine-DNA-methyltransferase or methylated-DNA-cysteine-S-methyltransferase) is a protein within the cell nucleus that is involved in the repair of alkylated DNA . MGMT is formed in all living things and in every body cell. In humans, the MGMT concentration is highest in the liver. Inactivation of the MGMT gene leads to tumor formation .

The methylation of DNA in addition to their advantages and disadvantages. For example, 6-O-methylguanine can be formed from guanine . This happens within the DNA and can lead to the formation of tumors . The repair of this defect is accomplished by MGMT by transferring the methyl group onto itself. Since MGMT is consumed in this reaction, it is not strictly an enzyme . The term suicide enzyme is used more often.

${\ displaystyle \ mathrm {\ {\ xrightarrow {MGMT}}}}$

Removal of the methyl group from 6- O -methylguanosine , formation of guanosine

The detection of epigenetic changes in the MGMT promoter (hypermethylation) goes with glioblastoma with a better prognosis and a better response to chemotherapy with alkylating agents such as temozolomide associated. DNA-based methods using strict quality control are suitable for the detection of MGMT promoter methylation for clinical purposes, but immunohistochemical protein detection is not.

Individual evidence

^ Stupp et al .: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005; 352: 987-996; PMID 15758009 .
^ Stupp et al .: Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomized phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009; 10 (5): 459-466; PMID 19269895 .
Jump up ↑ Preusser M , Charles Janzer R, Felsberg J, Reifenberger G, Hamou MF, Diserens AC, Stupp R, Gorlia T, Marosi C, Heinzl H, Hainfellner JA, Hegi M. Anti-O6-methylguanine-methyltransferase (MGMT) immunohistochemistry in glioblastoma multiforme: observer variability and lack of association with patient survival impede its use as clinical biomarker. Brain pathol. 2008 Oct; 18 (4): 520-32. doi : 10.1111 / j.1750-3639.2008.00153.x .
↑ Reifenberger G, Malzkorn B, Acker T, Bettstetter M, Buslei R, von Deimling A, Dietmaier W, Dubbink HJ, Eigenbrod S, Garvalov BK, Gerstenmaier U, Giese A, Haase D, Hasselblatt M, Kirches E, Koch A, Marienfeld R, Mittelbronn M, Montesinos-Rongen M, Pagenstecher A, Riemenschneider MJ, Prinz M, Romeike B, Roos A, Spiegl-Kreinecker S, Schittenhelm J, Schlegel J, Thal DR, Tops BB, Weis J, Westphal G, Worm K, Felsberg J. Results of the international interlaboratory comparison of mgmt promoter methylation analysis involving twenty-three academic centers in Germany, Austria and the Netherlands. Neuro Oncol. 2014 Jul; 16 Suppl 3: iii49-iii50. doi : 10.1093 / neuonc / nou209.30 .

Web links

O6 methylguanine DNA methyltransferase. In: Online Mendelian Inheritance in Man . (English)

[1] Stupp et al .: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005; 352: 987-996; PMID 15758009 .

[2] Stupp et al .: Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomized phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009; 10 (5): 459-466; PMID 19269895 .

[”P1”-3] Jump up ↑ Preusser M , Charles Janzer R, Felsberg J, Reifenberger G, Hamou MF, Diserens AC, Stupp R, Gorlia T, Marosi C, Heinzl H, Hainfellner JA, Hegi M. Anti-O6-methylguanine-methyltransferase (MGMT) immunohistochemistry in glioblastoma multiforme: observer variability and lack of association with patient survival impede its use as clinical biomarker. Brain pathol. 2008 Oct; 18 (4): 520-32. doi : 10.1111 / j.1750-3639.2008.00153.x .

[P20-4] Reifenberger G, Malzkorn B, Acker T, Bettstetter M, Buslei R, von Deimling A, Dietmaier W, Dubbink HJ, Eigenbrod S, Garvalov BK, Gerstenmaier U, Giese A, Haase D, Hasselblatt M, Kirches E, Koch A, Marienfeld R, Mittelbronn M, Montesinos-Rongen M, Pagenstecher A, Riemenschneider MJ, Prinz M, Romeike B, Roos A, Spiegl-Kreinecker S, Schittenhelm J, Schlegel J, Thal DR, Tops BB, Weis J, Westphal G, Worm K, Felsberg J. Results of the international interlaboratory comparison of mgmt promoter methylation analysis involving twenty-three academic centers in Germany, Austria and the Netherlands. Neuro Oncol. 2014 Jul; 16 Suppl 3: iii49-iii50. doi : 10.1093 / neuonc / nou209.30 .