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New page: '''Unreleased structure''' The entry 5llq is ON HOLD until Paper Publication Authors: Miggiano, R., Rossi, F., Rizzi, M. Description: Crystal structure of Sulfolobus solfataricus O6-me...
 
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'''Unreleased structure'''


The entry 5llq is ON HOLD  until Paper Publication
==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 [https://en.wikipedia.org/wiki/Saccharolobus_solfataricus_P2 Saccharolobus solfataricus P2]. 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 [https://proteopedia.org/fgij/fg.htm?mol=5LLQ 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]] 2.7&#8491;</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5llq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5llq OCA], [https://pdbe.org/5llq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5llq RCSB], [https://www.ebi.ac.uk/pdbsum/5llq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5llq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/OGT_SACS2 OGT_SACS2] Involved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) and O4-methylthymine (O4-MeT) in DNA. Repairs the methylated nucleobase in DNA by stoichiometrically transferring the methyl group to a cysteine residue in the enzyme. This is a suicide reaction: the enzyme is irreversibly inactivated.[HAMAP-Rule:MF_00772]
<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.


Authors: Miggiano, R., Rossi, F., Rizzi, M.
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>


Description: Crystal structure of Sulfolobus solfataricus O6-methylguanine methyltransferase C119F variant
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Rossi, F]]
<div class="pdbe-citations 5llq" style="background-color:#fffaf0;"></div>
[[Category: Miggiano, R]]
 
[[Category: Rizzi, M]]
==See Also==
*[[DNA methyltransferase 3D structures|DNA methyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharolobus solfataricus P2]]
[[Category: Miggiano R]]
[[Category: Rizzi M]]
[[Category: Rossi F]]
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