4RT2

Ternary complex crystal structure of DNA polymerase Beta with (alpha,beta)-CH2-(beta,gamma)-NH-dTTP

Summary for 4RT2

• Entry DOI: 10.2210/pdb4rt2/pdb
• Related: 4RT3
• Descriptor: DNA polymerase beta, DNA (5'-D(*CP*CP*GP*AP*CP*AP*GP*CP*GP*CP*AP*TP*CP*AP*GP*C)-3'), DNA (5'-D(*GP*CP*TP*GP*AP*TP*GP*CP*GP*(DOC))-3'), ... (9 entities in total)
• Functional Keywords: dna polymerase beta, conformational change, enzyme mechanism, transferase-dna complex, transferase/dna
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P06746
• Total number of polymer chains: 4
• Total formula weight: 48283.81

Authors

Batra, V.K.,Wilson, S.H. (deposition date: 2014-11-12, release date: 2015-07-01, Last modification date: 2023-09-20)

Primary citation

Kadina, A.P.,Kashemirov, B.A.,Oertell, K.,Batra, V.K.,Wilson, S.H.,Goodman, M.F.,McKenna, C.E.
Two Scaffolds from Two Flips: (alpha, beta)/(beta, gamma) CH2/NH "Met-Im" Analogues of dTTP.
Org.Lett., 17:2586-2589, 2015

PubMed Abstract: Novel α,β-CH2 and β,γ-NH (1a) or α,β-NH and β,γ-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 β, attributed to an NH-group interaction with R183 in the active site.

PubMed: 25970636
DOI: 10.1021/acs.orglett.5b00799

Experimental method

X-RAY DIFFRACTION (1.92 Å)