bioc441 - lecture 26.Deoxyribonucl

bioc441 - lecture 26.Deoxyribonucl - 26....

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26. Deoxyribonucleotide biosynthesis and nucleotide catabolism
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dTTP ADP GDP CDP UDP H 2 O NADP + NADPH ribonucleotide reductase X SH SH X S S Ribonucleotide reductase reduces ADP, GDP, DNA synthesis also requires thymine, which is made from dUDP. Regeneration of the reduced enzyme requires several steps Two cysteines in the enzyme serve as the reductant. OH OH O P -O- P -O-CH 2 N OH P -O- P -O-CH 2 O N dADP dGDP dCDP dUDP
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QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture. 1av8.pdb R2 dimer regulatory sites R2 R2 O O R1 R1 The enzyme has two types of subunits, R1 and R2. Each of the catalytic sites in ribonucleotide reductase has a binuclear Fe center and a stable tyrosyl radical O CHCH 2 C=O NH O O C Fe Fe C O O C O O N N N N C O O tyrosyl radical two Fe The catalytic sites are at the R1-R2 interfaces
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Ribonucleotide reductase generates free-radical intermediates NDP P -O- P -O-CH 2 N OH OH O H OH OH O P -O- P -O-CH 2 N H H X H SH SH OH P -O- P -O-CH 2 N O H + X H S S H OH O P -O- P -O-CH 2 N H H X SH SH X S S dNDP 1 2 3 The tyrosine radical generates another radical ( X ) close to the substrate. Most electron-transfer reactions of NADH involve hydride ion transfer. P -O- P -O-CH 2 N H OH O H H ) transfer Step 2: hydride ion ( H ) transfer or two 1-e reactions and H + OH - H +
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Two sets of redox proteins carry electrons from NADPH to ribonucleotide reductase (RNR) glutathione glutathione reductase glutaredoxin reductase X SH SH X S S NDP dNDP S S SH SH G SS G 2 G SH NADPH NADP + glutaredoxin CO 2 H 3 N-CH-CH 2 CH 2 -CO-NH-CH-CO-NH-CH 2 -CO 2 CH 2 SH + - - Glutathione ( γ -Glu-Cys-Gly) is the main redox buffer in the cytosol of most eukaryotic cells NADP + NADPH thioredoxin reductase (FAD) S S SH SH thioredoxin X SH SH X S S RNR RNR
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bioc441 - lecture 26.Deoxyribonucl - 26....

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