View source for 5llq


==Crystal structure of Sulfolobus solfataricus O6-methylguanine methyltransferase C119F variant==
<StructureSection load='5llq' size='340' side='right'caption='[[5llq]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5llq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Sacs2 Sacs2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LLQ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5LLQ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ogt, SSO2487 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=273057 SACS2])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Methylated-DNA--[protein]-cysteine_S-methyltransferase Methylated-DNA--[protein]-cysteine S-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.63 2.1.1.63] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5llq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5llq OCA], [http://pdbe.org/5llq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5llq RCSB], [http://www.ebi.ac.uk/pdbsum/5llq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5llq ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/OGT_SULSO OGT_SULSO]] Involved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) in DNA. Repairs alkylated guanine in DNA by stoichiometrically transferring the alkyl group at the O-6 position to a cysteine residue in the enzyme. This is a suicide reaction: the enzyme is irreversibly inactivated. 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
BACKGROUND: Alkylated DNA-protein alkyltransferases (AGTs) are conserved proteins that repair alkylation damage in DNA by using a single-step mechanism leading to irreversible alkylation of the catalytic cysteine in the active site. Trans-alkylation induces inactivation and destabilization of the protein, both in vitro and in vivo, likely triggering conformational changes. A complete picture of structural rearrangements occurring during the reaction cycle is missing, despite considerable interest raised by the peculiarity of AGT reaction, and the contribution of a functional AGT in limiting the efficacy of chemotherapy with alkylating drugs. METHODS: As a model for AGTs we have used a thermostable ortholog from the archaeon Sulfolobus solfataricus (SsOGT), performing biochemical, structural, molecular dynamics and in silico analysis of ligand-free, DNA-bound and mutated versions of the protein. RESULTS: Conformational changes occurring during lesion recognition and after the reaction, allowed us to identify a novel interaction network contributing to SsOGT stability, which is perturbed when a bulky adduct between the catalytic cysteine and the alkyl group is formed, a mandatory step toward the permanent protein alkylation. CONCLUSIONS: Our data highlighted conformational changes and perturbation of intramolecular interaction occurring during lesion recognition and catalysis, confirming our previous hypothesis that coordination between the N- and C-terminal domains of SsOGT is important for protein activity and stability. GENERAL SIGNIFICANCE: A general model of structural rearrangements occurring during the reaction cycle of AGTs is proposed. If confirmed, this model might be a starting point to design strategies to modulate AGT activity in therapeutic settings.

Interdomain interactions rearrangements control the reaction steps of a thermostable DNA alkyltransferase.,Morrone C, Miggiano R, Serpe M, Massarotti A, Valenti A, Del Monaco G, Rossi M, Rossi F, Rizzi M, Perugino G, Ciaramella M Biochim Biophys Acta. 2016 Oct 22;1861(2):86-96. doi:, 10.1016/j.bbagen.2016.10.020. PMID:27777086<ref>PMID:27777086</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 5llq" style="background-color:#fffaf0;"></div>

==See Also==
*[[DNA methyltransferase 3D structures|DNA methyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Sacs2]]
[[Category: Miggiano, R]]
[[Category: Rizzi, M]]
[[Category: Rossi, F]]
[[Category: Dna dealkylation]]
[[Category: Inactive mutant]]
[[Category: Ogt]]
[[Category: Transferase]]