4f21: Difference between revisions
No edit summary |
No edit summary |
||
| (9 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Crystal structure of carboxylesterase/phospholipase family protein from Francisella tularensis== | |||
<StructureSection load='4f21' size='340' side='right'caption='[[4f21]], [[Resolution|resolution]] 2.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4f21]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Francisella_tularensis_subsp._tularensis_SCHU_S4 Francisella tularensis subsp. tularensis SCHU S4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F21 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4F21 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]] 2.5Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0S1:N-((1R,2S)-2-ALLYL-4-OXOCYCLOBUTYL)-4-METHYLBENZENESULFONAMIDE,+BOUND+FORM'>0S1</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=4f21 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f21 OCA], [https://pdbe.org/4f21 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4f21 RCSB], [https://www.ebi.ac.uk/pdbsum/4f21 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4f21 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q5NI32_FRATT Q5NI32_FRATT] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Tularemia is a deadly, febrile disease caused by infection by the gram-negative bacterium, Francisella tularensis. Members of the ubiquitous serine hydrolase protein family are among current targets to treat diverse bacterial infections. Herein we present a structural and functional study of a novel bacterial carboxylesterase (FTT258) from F. tularensis, a homologue of human acyl protein thioesterase (hAPT1). The structure of FTT258 has been determined in multiple forms, and unexpectedly large conformational changes of a peripheral flexible loop occur in the presence of a mechanistic cyclobutanone ligand. The concomitant changes in this hydrophobic loop and the newly exposed hydrophobic substrate binding pocket suggest that the observed structural changes are essential to the biological function and catalytic activity of FTT258. Using diverse substrate libraries, site-directed mutagenesis, and liposome binding assays, we determined the importance of these structural changes to the catalytic activity and membrane binding activity of FTT258. Residues within the newly exposed hydrophobic binding pocket and within the peripheral flexible loop proved essential to the hydrolytic activity of FTT258, indicating that structural rearrangement is required for catalytic activity. Both FTT258 and hAPT1 also showed significant association with liposomes designed to mimic bacterial or human membranes, respectively, even though similar structural rearrangements for hAPT1 have not been reported. The necessity for acyl protein thioesterases to have maximal catalytic activity near the membrane surface suggests that these conformational changes in the protein may dually regulate catalytic activity and membrane association in bacterial and human homologues. | |||
Large scale structural rearrangement of a serine hydrolase from Francisella tularensis facilitates catalysis.,Filippova EV, Weston LA, Kuhn ML, Geissler B, Gehring AM, Armoush N, Adkins CT, Minasov G, Dubrovska I, Shuvalova L, Winsor JR, Lavis LD, Satchell KJ, Becker DP, Anderson WF, Johnson RJ J Biol Chem. 2013 Apr 12;288(15):10522-35. doi: 10.1074/jbc.M112.446625. Epub, 2013 Feb 19. PMID:23430251<ref>PMID:23430251</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4f21" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Francisella tularensis subsp. tularensis SCHU S4]] | |||
[[Category: Large Structures]] | |||
[[Category: Anderson WF]] | |||
[[Category: Armoush N]] | |||
[[Category: Becker DP]] | |||
[[Category: Dubrovska I]] | |||
[[Category: Filippova EV]] | |||
[[Category: Kiryukhina O]] | |||
[[Category: Kuhn M]] | |||
[[Category: Minasov G]] | |||
[[Category: Shuvalova L]] | |||
[[Category: Wawrzak Z]] | |||
[[Category: Winsor JR]] | |||
Latest revision as of 09:30, 17 October 2024
Crystal structure of carboxylesterase/phospholipase family protein from Francisella tularensisCrystal structure of carboxylesterase/phospholipase family protein from Francisella tularensis
Structural highlights
FunctionPublication Abstract from PubMedTularemia is a deadly, febrile disease caused by infection by the gram-negative bacterium, Francisella tularensis. Members of the ubiquitous serine hydrolase protein family are among current targets to treat diverse bacterial infections. Herein we present a structural and functional study of a novel bacterial carboxylesterase (FTT258) from F. tularensis, a homologue of human acyl protein thioesterase (hAPT1). The structure of FTT258 has been determined in multiple forms, and unexpectedly large conformational changes of a peripheral flexible loop occur in the presence of a mechanistic cyclobutanone ligand. The concomitant changes in this hydrophobic loop and the newly exposed hydrophobic substrate binding pocket suggest that the observed structural changes are essential to the biological function and catalytic activity of FTT258. Using diverse substrate libraries, site-directed mutagenesis, and liposome binding assays, we determined the importance of these structural changes to the catalytic activity and membrane binding activity of FTT258. Residues within the newly exposed hydrophobic binding pocket and within the peripheral flexible loop proved essential to the hydrolytic activity of FTT258, indicating that structural rearrangement is required for catalytic activity. Both FTT258 and hAPT1 also showed significant association with liposomes designed to mimic bacterial or human membranes, respectively, even though similar structural rearrangements for hAPT1 have not been reported. The necessity for acyl protein thioesterases to have maximal catalytic activity near the membrane surface suggests that these conformational changes in the protein may dually regulate catalytic activity and membrane association in bacterial and human homologues. Large scale structural rearrangement of a serine hydrolase from Francisella tularensis facilitates catalysis.,Filippova EV, Weston LA, Kuhn ML, Geissler B, Gehring AM, Armoush N, Adkins CT, Minasov G, Dubrovska I, Shuvalova L, Winsor JR, Lavis LD, Satchell KJ, Becker DP, Anderson WF, Johnson RJ J Biol Chem. 2013 Apr 12;288(15):10522-35. doi: 10.1074/jbc.M112.446625. Epub, 2013 Feb 19. PMID:23430251[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||