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| | ==Crystal structure of Cytochrome C Peroxidase W191G-Gateless in complex with N-methyl-1H-benzimidazol-2-amine== | | ==Crystal structure of Cytochrome C Peroxidase W191G-Gateless in complex with N-methyl-1H-benzimidazol-2-amine== |
| - | <StructureSection load='4jmz' size='340' side='right' caption='[[4jmz]], [[Resolution|resolution]] 1.82Å' scene=''> | + | <StructureSection load='4jmz' size='340' side='right'caption='[[4jmz]], [[Resolution|resolution]] 1.82Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4jmz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JMZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JMZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4jmz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_RM11-1a Saccharomyces cerevisiae RM11-1a]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JMZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JMZ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1M2:N-METHYL-1H-BENZIMIDAZOL-2-AMINE'>1M2</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1M2:N-METHYL-1H-BENZIMIDAZOL-2-AMINE'>1M2</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1kxn|1kxn]], [[1kxm|1kxm]], [[4jm5|4jm5]], [[4jm6|4jm6]], [[4jm8|4jm8]], [[4jm9|4jm9]], [[4jma|4jma]], [[4jmw|4jmw]], [[4jpl|4jpl]], [[4jpt|4jpt]], [[4jpu|4jpu]], [[4jqj|4jqj]], [[4jqk|4jqk]], [[4jqm|4jqm]], [[4jqn|4jqn]], [[4jmb|4jmb]], [[4jms|4jms]], [[4jmt|4jmt]], [[4jmv|4jmv]], [[4jn0|4jn0]]</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=4jmz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jmz OCA], [https://pdbe.org/4jmz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jmz RCSB], [https://www.ebi.ac.uk/pdbsum/4jmz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jmz ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CCP1 CCP CPO YKR066C, SCRG_04081 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=285006 Baker's yeast])</td></tr>
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| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cytochrome-c_peroxidase Cytochrome-c peroxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.1.5 1.11.1.5] </span></td></tr>
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4jmz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jmz OCA], [http://pdbe.org/4jmz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4jmz RCSB], [http://www.ebi.ac.uk/pdbsum/4jmz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4jmz ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/B3LRE1_YEAS1 B3LRE1_YEAS1] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Cytochrome c peroxidase|Cytochrome c peroxidase]] | + | *[[Cytochrome c peroxidase 3D structures|Cytochrome c peroxidase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Baker's yeast]] | + | [[Category: Large Structures]] |
| - | [[Category: Cytochrome-c peroxidase]] | + | [[Category: Saccharomyces cerevisiae RM11-1a]] |
| - | [[Category: Barelier, S]] | + | [[Category: Barelier S]] |
| - | [[Category: Fischer, M]] | + | [[Category: Fischer M]] |
| - | [[Category: Bulk solvent]]
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| - | [[Category: Docking]]
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| - | [[Category: Ligand binding]]
| + | |
| - | [[Category: Model system]]
| + | |
| - | [[Category: Ordered water]]
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| - | [[Category: Oxidoreductase]]
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| Structural highlights
Function
B3LRE1_YEAS1
Publication Abstract from PubMed
A key challenge in structure-based discovery is accounting for modulation of protein-ligand interactions by ordered and bulk solvent. To investigate this, we compared ligand binding to a buried cavity in Cytochrome c Peroxidase (CcP), where affinity is dominated by a single ionic interaction, versus a cavity variant partly opened to solvent by loop deletion. This opening had unexpected effects on ligand orientation, affinity, and ordered water structure. Some ligands lost over ten-fold in affinity and reoriented in the cavity, while others retained their geometries, formed new interactions with water networks, and improved affinity. To test our ability to discover new ligands against this opened site prospectively, a 534,000 fragment library was docked against the open cavity using two models of ligand solvation. Using an older solvation model that prioritized many neutral molecules, three such uncharged docking hits were tested, none of which was observed to bind; these molecules were not highly ranked by the new, context-dependent solvation score. Using this new method, another 15 highly-ranked molecules were tested for binding. In contrast to the previous result, 14 of these bound detectably, with affinities ranging from 8 microM to 2 mM. In crystal structures, four of these new ligands superposed well with the docking predictions but two did not, reflecting unanticipated interactions with newly ordered waters molecules. Comparing recognition between this open cavity and its buried analog begins to isolate the roles of ordered solvent in a system that lends itself readily to prospective testing and that may be broadly useful to the community.
Roles for ordered and bulk solvent in ligand recognition and docking in two related cavities.,Barelier S, Boyce SE, Fish I, Fischer M, Goodin DB, Shoichet BK PLoS One. 2013 Jul 18;8(7):e69153. doi: 10.1371/journal.pone.0069153. Print 2013. PMID:23874896[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Barelier S, Boyce SE, Fish I, Fischer M, Goodin DB, Shoichet BK. Roles for ordered and bulk solvent in ligand recognition and docking in two related cavities. PLoS One. 2013 Jul 18;8(7):e69153. doi: 10.1371/journal.pone.0069153. Print 2013. PMID:23874896 doi:10.1371/journal.pone.0069153
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