Ternary complex crystal structure of K289M variant of DNA polymerase Beta with "hot-spot sequence" with beta-gamma CF2 analogue of dGTP

Revealing an Internal Stabilization Deficiency in the DNA Polymerase beta K289M Cancer Variant through the Combined Use of Chemical Biology and X-ray Crystallography.

DNA (5'-D(*CP*CP*GP*AP*AP*CP*AP*AP*GP*CP*AP*TP*CP*AP*GP*C)-3')

DNA (5'-D(*GP*CP*TP*GP*AP*TP*GP*CP*TP*(2DT))-3')

MSKRKAPQETLNGGITDMLTELANFEKNVSQAIHKYNAYRKAASVIAKYPHKIKSGAEAKKLPGVGTKIAEKIDEFLATG
KLRKLEKIRQDDTSSSINFLTRVSGIGPSAARKFVDEGIKTLEDLRKNEDKLNHHQRIGLKYFGDFEKRIPREEMLQMQD
IVLNEVKKVDSEYIATVCGSFRRGAESSGDMDVLLTHPSFTSESTKQPKLLHQVVEQLQKVHFITDTLSKGETKFMGVCQ
LPSKNDEKEYPHRRIDIRLIPKDQYYCGVLYFTGSDIFNKNMRAHALEMGFTINEYTIRPLGVTGVAGEPLPVDSEKDIF
DYIQWKYREPKDRSE

7.5, 50 mM Imidazole, 350 mM Sodium Acetate

DNA Polymerase Beta, Conformational Change, enzyme mechanism, LFER, transcription-dna complex

MSKRKAPQETLNGGITDMLTELANFEKNVSQAIHKYNAYRKAASVIAKYPHKIKSGAEAKKLPGVGTKIAEKIDEFLATG
KLRKLEKIRQDDTSSSINFLTRVSGIGPSAARKFVDEGIKTLEDLRKNEDKLNHHQRIGLKYFGDFEKRIPREEMLQMQD
IVLNEVKKVDSEYIATVCGSFRRGAESSGDMDVLLTHPSFTSESTKQPKLLHQVVEQLQKVHFITDTLSKGETKFMGVCQ
LPSKNDEKEYPHRRIDIRLIPKDQYYCGVLYFTGSDIFNKNMRAHALEKGFTINEYTIRPLGVTGVAGEPLPVDSEKDIF
DYIQWKYREPKDRSE