2fld: Difference between revisions
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<StructureSection load='2fld' size='340' side='right'caption='[[2fld]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='2fld' size='340' side='right'caption='[[2fld]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2fld]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2fld]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Monomastix_sp._OKE-1 Monomastix sp. OKE-1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FLD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FLD FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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=2fld FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fld OCA], [https://pdbe.org/2fld PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fld RCSB], [https://www.ebi.ac.uk/pdbsum/2fld PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fld ProSAT]</span></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=2fld FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fld OCA], [https://pdbe.org/2fld PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fld RCSB], [https://www.ebi.ac.uk/pdbsum/2fld PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fld ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/C0JWR6_MONSK C0JWR6_MONSK] | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Monomastix sp. OKE-1]] | ||
[[Category: Ashworth | [[Category: Ashworth J]] | ||
[[Category: Baker | [[Category: Baker D]] | ||
[[Category: Duarte | [[Category: Duarte CM]] | ||
[[Category: Havranek | [[Category: Havranek JJ]] | ||
[[Category: Monnat | [[Category: Monnat RJ]] | ||
[[Category: Stoddard | [[Category: Stoddard BL]] | ||
[[Category: Sussman | [[Category: Sussman D]] | ||
Latest revision as of 12:28, 30 August 2023
I-MsoI Re-Designed for Altered DNA Cleavage SpecificityI-MsoI Re-Designed for Altered DNA Cleavage Specificity
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe reprogramming of DNA-binding specificity is an important challenge for computational protein design that tests current understanding of protein-DNA recognition, and has considerable practical relevance for biotechnology and medicine. Here we describe the computational redesign of the cleavage specificity of the intron-encoded homing endonuclease I-MsoI using a physically realistic atomic-level forcefield. Using an in silico screen, we identified single base-pair substitutions predicted to disrupt binding by the wild-type enzyme, and then optimized the identities and conformations of clusters of amino acids around each of these unfavourable substitutions using Monte Carlo sampling. A redesigned enzyme that was predicted to display altered target site specificity, while maintaining wild-type binding affinity, was experimentally characterized. The redesigned enzyme binds and cleaves the redesigned recognition site approximately 10,000 times more effectively than does the wild-type enzyme, with a level of target discrimination comparable to the original endonuclease. Determination of the structure of the redesigned nuclease-recognition site complex by X-ray crystallography confirms the accuracy of the computationally predicted interface. These results suggest that computational protein design methods can have an important role in the creation of novel highly specific endonucleases for gene therapy and other applications. Computational redesign of endonuclease DNA binding and cleavage specificity.,Ashworth J, Havranek JJ, Duarte CM, Sussman D, Monnat RJ Jr, Stoddard BL, Baker D Nature. 2006 Jun 1;441(7093):656-9. PMID:16738662[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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