A nucleoside with one or more phosphate groups attached to the sugar is called a nucleotide. The name of a nucleotide is the corresponding nucleoside name, followed by the word 'monophosphate,' 'diphosphate,' or 'triphosphate' to indicate the number of phosphate groups attached to the sugar.
Click the button below to examine the structure of a nucleotide triphosphate. What is the identity of the nucleotide triphosphate displayed in the computer model? Adenosine triphosphate ATP. Deoxyadenosine triphosphate dATP. Guanosine triphosphate GTP.
Deoxyguanosine triphosphate dGTP. Thymidine triphosphate TTP. Click the button below to examine the structure of deoxyadenine monosphosphate dAMP. Notice the angle of the sugar and phosphate groups in relation to the planar nitrogenous base. In double-stranded DNA, two long molecules twist around one another in a double helix. These molecules are d eoxy n ucleic a cids DNA : polymers made up of nucleotides In a DNA double helix, the phosphate and sugar groups make up the outer 'backbones,' and the flat nitrogenous bases are pointed toward the middle of the helix.
Click the buttons below to examine a segment of a DNA double helix from many angles. The first button has colored the backbone sugar and phosphate groups purple to simplify the image. One key point to notice in the DNA double helix structure is that the planar nitrogenous bases from the two strands are pointing toward each other, in the middle of the helix.
Find more information on the Altmetric Attention Score and how the score is calculated. Recently, Vakonakis and LiWang J. We have analyzed the proposed correlation between NMR shielding and hydrogen-bond strength using density functional theory. Although we agree with the conclusion that A:U is more strongly bound, we find no correlation between the hydrogen-bond strength and the NMR shielding of C2.
In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed. Cartesian coordinates, NMR shielding constants, and bond energy decomposition for all base pairs, including an assessment of how these quantities are affected by basis-set size effects, the performance of density functionals, relativistic effects, solvent effects, and variations of base pair geometries.
Such files may be downloaded by article for research use if there is a public use license linked to the relevant article, that license may permit other uses. View Author Information. Cite this: J. Article Views Altmetric -. Citations Supporting Information Available. Cited By. This article is cited by 75 publications. Ben Joseph R. Journal of Chemical Information and Modeling , 61 1 , The Journal of Physical Chemistry B , 47 , The Journal of Organic Chemistry , 84 22 , Waggoner, Sidney M.
Hecht, Shengxi Chen. ACS Infectious Diseases , 5 11 , Seelam, Dhananjay Bhattacharyya, Abhijit Mitra. ACS Omega , 4 4 , Natalia C. The Journal of Physical Chemistry Letters , 9 13 , The Journal of Physical Chemistry B , 17 , Parker , Edward G. Hohenstein , Robert M. Parrish , Nicholas V. Hud , and C.
David Sherrill. Journal of the American Chemical Society , 4 , Nibbering , and Thomas Elsaesser. The Journal of Physical Chemistry A , 3 , The Journal of Physical Chemistry A , 7 , Petrov , and Neocles B. The Journal of Physical Chemistry B , 48 , Requena , E. Michaux , D. The Journal of Physical Chemistry B , 42 , Inorganic Chemistry , 49 6 , A conserved leucine human L , positioned directly above the uracil-binding pocket, was suggested as a candidate to assist the local melting of the DNA helix Mol et al.
Furthermore, compression of the backbone flanking uracil was for the first time implicated in catalysis, assisted by extensive conformational changes in the enzyme upon formation of the productive complex.
In the LA mutant structure the uracil had dissociated, and the enzyme rebound to the product, an extrahelically positioned AP-site. This implied that the extrahelical conformation could be achieved even in the absence of the insertion of a hydrophobic side chain push.
More recent data, however, indicate that the function of the inserting leucine side chain may be more complex than merely pushing the uracil out of the double helix.
When analysing kinetic parameters of E. Using stopped-flow experiments of E. When considering the energy contribution of each discrete event above to the overall catalytic reaction, one should bear in mind that DNA is a very heterogeneous substrate.
This is also reflected by the different efficiency whereby uracil is excized from different sequence contexts Eftedal et al. Recently the sequence specificity was re-examined using both single-stranded and duplex DNA substrates Bellamy and Baldwin, , and the authors conclude that the observed variations were not due to stability of the uracil itself within the DNA structure.
Rather, local structure perturbations could affect uracil recognition, e. Uracil binding induces considerable conformational changes in UNG, bringing key residues in optimal distances to favour catalysis Slupphaug et al. This is accompanied by large conformational strain induced upon the deoxyuridine Parikh et al.
The developing negative charge at O2 is enzymatically stabilized by a neutral histidine E. Moreover, recent quantum- and molecular-mechanical calculations indicate that negative phosphate charges in the substrate itself may repel the anionic leaving group, and thus make a major contribution to the catalytic rate Dinner et al.
The authors suggest that such substrate autocatalysis may emerge as a general feature of DNA glycosylases. The observation that UNG had an higher affinity for the product AP-site than the actual substrate itself Parikh et al. Such rebinding has subsequently been observed for several DNA glycosylases Vidal et al. Perhaps the least understood stage in the processing of uracil-DNA is how the glycosylases recognize these subtle lesions within vast stretches of DNA. This is further complicated by the fact that eukaryotic DNA is organized in complex nucleoprotein structures.
In vitro , the UNG-proteins appear to function in both a processive and distributive fashion, depending on the salt concentration Bennett et al.
When a uracil residue is encountered, the mechanism of initial recognition is not obvious. Thus, the enzyme might instead flip every DNA base to probe against the specificity pocket. How the energetic cost of such a scanning mechanism is covered merits further investigation, however. SMUG1 removes uracil, as well as 5-hydroxymethyluracil 5-hmeU , from single- and double stranded DNA and is proposed to have an important role in removal of uracil resulting from cytosine deamination Nilsen et al.
SMUG1 is not thought to have a role in removal of incorporated uracil and it does not accumulate in replication foci. This procedure comprised in vitro expression from a library of cDNA, and electrophoretic mobility shift upon binding of damage-recognising protein to DNA containing modified nucleotides designed to target the active site of the glycosylases. The human counterpart was identified from EST databases Haushalter et al. Thus, genes for three out of four uracil-removing activities are located on chromosome The phylogeny of the uracil-DNA glycosylase genes will be discussed in more detail below.
Thus, the term single-strand selective is not entirely appropriate for the human enzyme. Furthermore, the xSMUG1 activity was not inhibited by the peptide inhibitor Ugi that efficiently inhibits both prokaryotic and eukaryotic uracil-DNA glycosylases belonging to the Ung -family.
However, it may also be formed in a two-step reaction; first the methyl-group of 5-meC in CpG-contexts is oxidised to 5-hmeC, and subsequently this residue is deaminated to yield 5-hmeU Cannon Carlson et al.
Even in extracts from wild-type mice, mSMUG1 contributed a substantial fraction of the total UDG-activity under these assay conditions. In the presence of 7. The situation may be different in mouse.
In conclusion, hSMUG1 is a non-abundant enzyme present in the nucleoplasm. The major function may be in removal of 5hmU and deaminated cytosines, although it may be less important than UNG2 in the latter process, at least in human cells.
This enzyme has a strict requirement for double-stranded substrates Baker et al. Thus, there are apparently at least three different human enzymatic activities for removal of 5-hmeU from DNA. However, the major physiological role of TDG remains elusive. Interestingly, TDG may also function as a transcription factor Hardeland et al. It does not cleave the DNA backbone, and thus contains no lyase activity Neddermann et al.
This is unexpected since TDG is generally very double-strand-specific, and since the substrate recognition, as deduced from data on the homologous bacterial protein MUG, involves interactions with both strands Barrett et al. In the cases described above, the substrate is a base that has been modified. O 6 meG in the template may direct incorporation of either C or T.
The rate-limiting step in the mechanism in vitro is the release of the product e. Recent findings indicate, however, that the AP-site binding capacity of TDG might be subject to regulation. Hardeland et al. The authors propose that TDG binds its substrate in the unmodified state, and that subsequent to catalysis, sumoylation allows detachment from the product AP-site.
Interestingly, a sumoylation consensus site is also present in MBD4 MED1 , but the functional implications of this remain to be established. However, they appear to have very similar structures. The structure of the bacterial homologue MUG has been solved Barrett et al.
Both enzymes are traversed by a DNA-binding groove connecting to a uracil-binding pocket, which in the case of MUG is less tailor-made for uracil. Two active site motifs are conserved. These are identical in human, E. In both cases, the base can only be accommodated in the catalytic pocket after the nucleotide is flipped out of the helix.
In the corresponding position in MUG, the amino acid is Gly20 which does not represent a major barrier to thymine. However, the Ser side chain is free to rotate. The smaller side chain of Ala represents an even smaller barrier to binding of T. These extensions may be involved in subcellular sorting and protein—protein interactions, although this has not yet been demonstrated. RAR and RXR are intracellular receptors that after binding of ligand function as transcription factors. Furthermore, TDG has been shown to be a strong repressor of thyroid transcription factor-1 TTF-1 transcriptional activity Missero et al.
Whether the transcription-associated activity of TDG is modulated by sumoylation is presently not known. This, however merits further investigation, since several transcription factors appear to be directly or indirectly regulated by sumoylation reviewed by Muller et al. In addition, it may function as a transcription factor.
Which of these functions is the most important remains unclear. MBD4 may also have an additional role in mismatch repair through its interaction with MLH1 reviewed in Bellacosa, Jump to site search. You do not have JavaScript enabled. Please enable JavaScript to access the full features of the site or access our non-JavaScript page. Issue 42, From the journal: Physical Chemistry Chemical Physics. You have access to this article.
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