View source for 4i2b


==Ternary complex of mouse TdT with ssDNA and AMPcPP==
<StructureSection load='4i2b' size='340' side='right'caption='[[4i2b]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4i2b]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I2B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4I2B FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=APC:DIPHOSPHOMETHYLPHOSPHONIC+ACID+ADENOSYL+ESTER'>APC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4i2b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i2b OCA], [https://pdbe.org/4i2b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4i2b RCSB], [https://www.ebi.ac.uk/pdbsum/4i2b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4i2b ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TDT_MOUSE TDT_MOUSE] Template-independent DNA polymerase which catalyzes the random addition of deoxynucleoside 5'-triphosphate to the 3'-end of a DNA initiator. One of the in vivo functions of this enzyme is the addition of nucleotides at the junction (N region) of rearranged Ig heavy chain and T-cell receptor gene segments during the maturation of B- and T-cells.
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== Publication Abstract from PubMed ==
Terminal deoxynucleotidyltransferase (Tdt) is a non-templated eukaryotic DNA polymerase of the polX family that is responsible for the random addition of nucleotides at the V(D)J junctions of immunoglobulins and T-cell receptors. Here we describe a series of high-resolution X-ray structures that mimic the pre-catalytic state, the post-catalytic state and a competent state that can be transformed into the two other ones in crystallo via the addition of dAMPcPP and Zn2+, respectively. We examined the effect of Mn2+, Co2+ and Zn2+ because they all have a marked influence on the kinetics of the reaction. All our data can be explained by a dynamic role of divalent transition metal ions bound to site A: (i) Zn2+ (or Co2+) in metal A site changes coordination to a tetrahedral state after the chemical step, which explains the higher affinity of Tdt for the primer strand, and (ii) metal A has to leave to allow the translocation of the primer strand and to clear the active site, a typical feature for a ratchet-like mechanism. Except for Zn2+, the sugar puckering of the primer strand 3' terminus changes from C2'-endo to C3'-endo during catalysis. In addition, our data are compatible with a scheme where metal A is the last component that binds to the active site to complete its productive assembly, as already inferred in human pol beta. The new structures have potential implications for modeling pol mu, a closely related polX implicated in the repair of DNA double-strand breaks, in a complex with a DNA synapsis.

Structures of Intermediates along the Catalytic Cycle of Terminal Deoxynucleotidyltransferase: Dynamical Aspects of the Two-Metal Ion Mechanism.,Gouge J, Rosario S, Romain F, Beguin P, Delarue M J Mol Biol. 2013 Jul 13. pii: S0022-2836(13)00441-5. doi:, 10.1016/j.jmb.2013.07.009. PMID:23856622<ref>PMID:23856622</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4i2b" style="background-color:#fffaf0;"></div>

==See Also==
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Delarue M]]
[[Category: Gouge J]]