2fj0: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Crystal Structure of Juvenile Hormone Esterase from Manduca sexta, with OTFP covalently attached== | ==Crystal Structure of Juvenile Hormone Esterase from Manduca sexta, with OTFP covalently attached== | ||
<StructureSection load='2fj0' size='340' side='right' caption='[[2fj0]], [[Resolution|resolution]] 2.70Å' scene=''> | <StructureSection load='2fj0' size='340' side='right' caption='[[2fj0]], [[Resolution|resolution]] 2.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2fj0]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2fj0]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Carolina_sphinx Carolina sphinx]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FJ0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2FJ0 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TFC:1,1,1-TRIFLUORO-3-(OCTYLTHIO)ACETONE'>TFC</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TFC:1,1,1-TRIFLUORO-3-(OCTYLTHIO)ACETONE'>TFC</scene></td></tr> | ||
<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=2fj0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fj0 OCA], [http://pdbe.org/2fj0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2fj0 RCSB], [http://www.ebi.ac.uk/pdbsum/2fj0 PDBsum]</span></td></tr> | <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=2fj0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fj0 OCA], [http://pdbe.org/2fj0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2fj0 RCSB], [http://www.ebi.ac.uk/pdbsum/2fj0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2fj0 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
| Line 10: | Line 11: | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fj/2fj0_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fj/2fj0_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
| Line 29: | Line 30: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Carolina sphinx]] | ||
[[Category: Wilson, D K]] | [[Category: Wilson, D K]] | ||
[[Category: Wogulis, M]] | [[Category: Wogulis, M]] | ||
Revision as of 11:58, 14 June 2018
Crystal Structure of Juvenile Hormone Esterase from Manduca sexta, with OTFP covalently attachedCrystal Structure of Juvenile Hormone Esterase from Manduca sexta, with OTFP covalently attached
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedJuvenile hormone (JH) is an insect hormone containing an alpha,beta-unsaturated ester consisting of a small alcohol and long, hydrophobic acid. JH degradation is required for proper insect development. One pathway of this degradation is through juvenile hormone esterase (JHE), which cleaves the JH ester bond to produce methanol and JH acid. JHE is a member of the functionally divergent alpha/beta-hydrolase family of enzymes and is a highly efficient enzyme that cleaves JH at very low in vivo concentrations. We present here a 2.7 A crystal structure of JHE from the tobacco hornworm Manduca sexta (MsJHE) in complex with the transition state analogue inhibitor 3-octylthio-1,1,1-trifluoropropan-2-one (OTFP) covalently bound to the active site. This crystal structure, the first JHE structure reported, contains a long, hydrophobic binding pocket with the solvent-inaccessible catalytic triad located at the end. The structure explains many of the interactions observed between JHE and its substrates and inhibitors, such as the preference for small alcohol groups and long hydrophobic backbones. The most potent JHE inhibitors identified to date contain a trifluoromethyl ketone (TFK) moiety and have a sulfur atom beta to the ketone. In this study, sulfur-aromatic interactions were observed between the sulfur atom of OTFP and a conserved aromatic residue in the crystal structure. Mutational analysis supported the hypothesis that these interactions contribute to the potency of sulfur-containing TFK inhibitors. Together, these results clarify the binding mechanism of JHE inhibitors and provide useful observations for the development of additional enzyme inhibitors for a variety of enzymes. Structural studies of a potent insect maturation inhibitor bound to the juvenile hormone esterase of Manduca sexta.,Wogulis M, Wheelock CE, Kamita SG, Hinton AC, Whetstone PA, Hammock BD, Wilson DK Biochemistry. 2006 Apr 4;45(13):4045-57. PMID:16566578[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||