4rt2
From Proteopedia
Ternary complex crystal structure of DNA polymerase Beta with (alpha,beta)-CH2-(beta,gamma)-NH-dTTP
Structural highlights
Function[DPOLB_HUMAN] Repair polymerase that plays a key role in base-excision repair. Has 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity that removes the 5' sugar phosphate and also acts as a DNA polymerase that adds one nucleotide to the 3' end of the arising single-nucleotide gap. Conducts 'gap-filling' DNA synthesis in a stepwise distributive fashion rather than in a processive fashion as for other DNA polymerases.[1] [2] [3] [4] Publication Abstract from PubMedNovel alpha,beta-CH2 and beta,gamma-NH (1a) or alpha,beta-NH and beta,gamma-CH2 (1b) "Met-Im" dTTPs were synthesized via monodemethylation of triethyl-dimethyl phosphorimido-bisphosphonate synthons (4a, 4b), formed via a base-induced [1,3]-rearrangement of precursors (3a, 3b) in a reaction with dimethyl or diethyl phosphochloridate. Anomerization during final bromotrimethylsilane (BTMS) deprotection after Mitsunobu conjugation with dT was avoided by microwave conditions. 1a was 9-fold more potent in inhibiting DNA polymerase beta, attributed to an NH-group interaction with R183 in the active site. Two Scaffolds from Two Flips: (alpha,beta)/(beta,gamma) CH2/NH "Met-Im" Analogues of dTTP.,Kadina AP, Kashemirov BA, Oertell K, Batra VK, Wilson SH, Goodman MF, McKenna CE Org Lett. 2015 Jun 5;17(11):2586-9. doi: 10.1021/acs.orglett.5b00799. Epub 2015, May 13. PMID:25970636[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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