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== | ==Crystal structure of S. marcescens chitinase B in complex with the cyclic dipeptide inhibitor cyclo-(His-L-Pro) at 1.9 A resolution== | ||
Family 18 chitinases play an essential role in a range of pathogens and | <StructureSection load='1w1t' size='340' side='right'caption='[[1w1t]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1w1t]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Serratia_marcescens Serratia marcescens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W1T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W1T 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]] 1.9Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CHQ:CYCLO-(L-HISTIDINE-L-PROLINE)+INHIBITOR'>CHQ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1w1t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w1t OCA], [https://pdbe.org/1w1t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w1t RCSB], [https://www.ebi.ac.uk/pdbsum/1w1t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w1t ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q54276_SERMA Q54276_SERMA] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/w1/1w1t_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1w1t ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Family 18 chitinases play an essential role in a range of pathogens and pests. Several inhibitors are known, including the potent inhibitors argadin and allosamidin, and the structures of these in complex with chitinases have been elucidated. Recent structural analysis has revealed that CI-4 [cyclo-(L-Arg-D-Pro)] inhibits family 18 chitinases by mimicking the structure of the proposed reaction intermediate. Here we report the high-resolution structures of four new CI-4 derivatives, cyclo-(L-Arg-L-Pro), cyclo-(Gly-L-Pro), cyclo-(L-His-L-Pro), and cyclo-(L-Tyr-L-Pro), in complex with a family 18 chitinase. In addition, details of enzyme inhibition and in vivo activity against Saccharomyces cerevisiae are presented. The structures reveal that the common cyclo-(Gly-Pro) substructure is sufficient for binding, allowing modification of the side chain of the nonproline residue. This suggests that design of cyclic dipeptides with a view to increasing inhibition of family 18 chitinases should be possible through relatively accessible chemistry. The derivatives presented here in complex with chitinase B from Serratia marcescens provide further insight into the mechanism of inhibition of chitinases by cyclic dipeptides as well as providing a new scaffold for chitinase inhibitor design. | |||
Structure-based exploration of cyclic dipeptide chitinase inhibitors.,Houston DR, Synstad B, Eijsink VG, Stark MJ, Eggleston IM, van Aalten DM J Med Chem. 2004 Nov 4;47(23):5713-20. PMID:15509170<ref>PMID:15509170</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[Category: | <div class="pdbe-citations 1w1t" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Chitinase 3D structures|Chitinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Serratia marcescens]] | [[Category: Serratia marcescens]] | ||
[[Category: Eggleston I]] | |||
[[Category: Eijsink VGH]] | |||
[[Category: Eggleston | [[Category: Houston DR]] | ||
[[Category: Eijsink | [[Category: Synstad B]] | ||
[[Category: Houston | [[Category: Van Aalten DMF]] | ||
[[Category: Synstad | |||
[[Category: | |||
Latest revision as of 16:12, 13 December 2023
Crystal structure of S. marcescens chitinase B in complex with the cyclic dipeptide inhibitor cyclo-(His-L-Pro) at 1.9 A resolutionCrystal structure of S. marcescens chitinase B in complex with the cyclic dipeptide inhibitor cyclo-(His-L-Pro) at 1.9 A resolution
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 PubMedFamily 18 chitinases play an essential role in a range of pathogens and pests. Several inhibitors are known, including the potent inhibitors argadin and allosamidin, and the structures of these in complex with chitinases have been elucidated. Recent structural analysis has revealed that CI-4 [cyclo-(L-Arg-D-Pro)] inhibits family 18 chitinases by mimicking the structure of the proposed reaction intermediate. Here we report the high-resolution structures of four new CI-4 derivatives, cyclo-(L-Arg-L-Pro), cyclo-(Gly-L-Pro), cyclo-(L-His-L-Pro), and cyclo-(L-Tyr-L-Pro), in complex with a family 18 chitinase. In addition, details of enzyme inhibition and in vivo activity against Saccharomyces cerevisiae are presented. The structures reveal that the common cyclo-(Gly-Pro) substructure is sufficient for binding, allowing modification of the side chain of the nonproline residue. This suggests that design of cyclic dipeptides with a view to increasing inhibition of family 18 chitinases should be possible through relatively accessible chemistry. The derivatives presented here in complex with chitinase B from Serratia marcescens provide further insight into the mechanism of inhibition of chitinases by cyclic dipeptides as well as providing a new scaffold for chitinase inhibitor design. Structure-based exploration of cyclic dipeptide chitinase inhibitors.,Houston DR, Synstad B, Eijsink VG, Stark MJ, Eggleston IM, van Aalten DM J Med Chem. 2004 Nov 4;47(23):5713-20. PMID:15509170[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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