4k4h

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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4k4h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k4h OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4k4h RCSB], [http://www.ebi.ac.uk/pdbsum/4k4h PDBsum]</span></td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4k4h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k4h OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4k4h RCSB], [http://www.ebi.ac.uk/pdbsum/4k4h PDBsum]</span></td></tr>
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== Publication Abstract from PubMed ==
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Although lamivudine and emtricitabine, two L-deoxycytidine analogs, have been widely used as antiviral drugs for years, a structural basis for D-stereoselectivity against L-dNTPs, enantiomers of natural nucleotides (D-dNTPs), by any DNA polymerase or reverse transcriptase has not been established due to lack of a ternary structure of a polymerase, DNA, and an incoming L-dNTP. Here, we report 2.10-2.25 A ternary crystal structures of human DNA polymerase lambda, DNA, and L-deoxycytidine 5'-triphosphate (L-dCTP), or the triphosphates of lamivudine ((-)3TC-TP) and emtricitabine ((-)FTC-TP) with four ternary complexes per asymmetric unit. The structures of these 12 ternary complexes reveal that relative to D-deoxycytidine 5'-triphosphate (D-dCTP) in the canonical ternary structure of Pollambda-DNA-D-dCTP, L-dCTP, (-)3TC-TP, and (-)FTC-TP all have their ribose rotated by 180 degrees . Among the four ternary complexes with a specific L-nucleotide, two are similar and show that the L-nucleotide forms three Watson-Crick hydrogen bonds with the templating nucleotide dG and adopts a chair-like triphosphate conformation. In the remaining two similar ternary complexes, the L-nucleotide surprisingly interacts with the side chain of a conserved active site residue R517 through one or two hydrogen bonds, whereas the templating dG is anchored by a hydrogen bond with the side chain of a semiconserved residue Y505. Furthermore, the triphosphate of the L-nucleotide adopts an unprecedented N-shaped conformation. Our mutagenic and kinetic studies further demonstrate that the side chain of R517 is critical for the formation of the abovementioned four complexes along proposed catalytic pathways for L-nucleotide incorporation and provide the structural basis for the D-stereoselectivity of a DNA polymerase.
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Structural basis for the binding and incorporation of nucleotide analogs with L-stereochemistry by human DNA polymerase lambda,Vyas R, Zahurancik WJ, Suo Z Proc Natl Acad Sci U S A. 2014 Jul 11. pii: 201401286. PMID:25015085<ref>PMID:25015085</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
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<references/>
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Revision as of 06:34, 30 July 2014

Ternary crystal structures of a human DNA POLYMERASE LAMBDA IN COMPLEX WITH DNA AND (-)3TC-TP.

4k4h, resolution 2.10Å

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