View source for 9ics

[[Image:9ics.gif|left|200px]]

 {{Structure
|PDB= 9ics |SIZE=350|CAPTION= <scene name='initialview01'>9ics</scene>, resolution 2.900&Aring;
|SITE= 
|LIGAND= <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene> and <scene name='pdbligand=DCT:2&#39;,3&#39;-DIDEOXYCYTIDINE 5&#39;-TRIPHOSPHATE'>DCT</scene>
|ACTIVITY= 
|GENE= 
}}

'''DNA POLYMERASE BETA (E.C.2.7.7.7)/DNA COMPLEX + 2',3'-DIDEOXYCYTIDINE-5'-TRIPHOSPHATE, SOAKED IN THE PRESENCE OF DDCTP AND MNCL2'''


==Overview==
When crystals of human DNA polymerase beta (pol beta) complexed with DNA [Pelletier, H., Sawaya, M. R., Wolfle, W., Wilson, S. H., &amp; Kraut, J. (1996) Biochemistry 35, 12742-12761] are soaked in the presence of dATP and Mn2+, X-ray structural analysis shows that nucleotidyl transfer to the primer 3'-OH takes place directly in the crystals, even though the DNA is blunt-ended at the active site. Under similar crystal-soaking conditions, there is no evidence for a reaction when Mn2+ is replaced by Mg2+, which is thought to be the divalent metal ion utilized by most polymerases in vivo. These results suggest that one way Mn2+ may manifest its mutagenic effect on polymerases is by promoting greater reactivity than Mg2+ at the catalytic site, thereby allowing the nucleotidyl transfer reaction to take place with little or no regard to instructions from a template. Non-template-directed nucleotidyl transfer is also observed when pol beta-DNA cocrystals are soaked in the presence of dATP and Zn2+, but the reaction products differ in that the sugar moiety of the incorporated nucleotide appears distorted or otherwise cleaved, in agreement with reports that Zn2+ may act as a polymerase inhibitor rather than as a mutagen [Sirover, M. A., &amp; Loeb, L. A. (1976) Science 194, 1434-1436]. Although no reaction is observed when crystals are soaked in the presence of dATP and other metal ions such as Ca2+, Co2+, Cr3+, or Ni2+, X-ray structural analyses show that these metal ions coordinate the triphosphate moiety of the nucleotide in a manner that differs from that observed with Mg2+. In addition, all metal ions tested, with the exception of Mg2+, promote a change in the side-chain position of aspartic acid 192, which is one of three highly conserved active-site carboxylate residues. Soaking experiments with nucleotides other than dATP (namely, dCTP, dGTP, dTTP, ATP, ddATP, ddCTP, AZT-TP, and dATP alpha S) reveal a non-base-specific binding site on pol beta for the triphosphate and sugar moieties of a nucleotide, suggesting a possible mechanism for nucleotide selectivity whereby triphosphate-sugar binding precedes a check for correct base pairing with the template.

==About this Structure==
9ICS is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9ICS OCA]. 

==Reference==
A structural basis for metal ion mutagenicity and nucleotide selectivity in human DNA polymerase beta., Pelletier H, Sawaya MR, Wolfle W, Wilson SH, Kraut J, Biochemistry. 1996 Oct 1;35(39):12762-77. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8841119 8841119]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Pelletier, H.]]
[[Category: Sawaya, M R.]]
[[Category: DCT]]
[[Category: MN]]
[[Category: NA]]
[[Category: complex (nucleotidyltransferase/dna)]]
[[Category: dna repair]]
[[Category: dna replication]]
[[Category: dna-directed dna polymerase]]
[[Category: nucleotidyltransferase]]

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