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== | ==Complex of a chitinase with the natural product cyclopentapeptide argadin from Clonostachys== | ||
Over the past years, family 18 chitinases have been validated as potential | <StructureSection load='1h0g' size='340' side='right'caption='[[1h0g]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1h0g]] is a 4 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=1H0G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H0G 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]] 2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0AR:N-[N-[(4S)-4-AZANYL-5-HYDROXY-5-OXO-PENTYL]CARBAMIMIDOYL]ETHANAMIDE'>0AR</scene>, <scene name='pdbligand=DPR:D-PROLINE'>DPR</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HSE:L-HOMOSERINE'>HSE</scene>, <scene name='pdbligand=UN1:2-AMINOHEXANEDIOIC+ACID'>UN1</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=1h0g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h0g OCA], [https://pdbe.org/1h0g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h0g RCSB], [https://www.ebi.ac.uk/pdbsum/1h0g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h0g ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CHIB_SERMA CHIB_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/h0/1h0g_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=1h0g ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Over the past years, family 18 chitinases have been validated as potential targets for the design of drugs against human pathogens that contain or interact with chitin during their normal life cycles. Thus far, only one potent chitinase inhibitor has been described in detail, the pseudotrisaccharide allosamidin. Recently, however, two potent natural-product cyclopentapeptide chitinase inhibitors, argifin and argadin, were reported. Here, we describe high-resolution crystal structures that reveal the details of the interactions of these cyclopeptides with a family 18 chitinase. The structures are examples of complexes of a carbohydrate-processing enzyme with high-affinity peptide-based inhibitors and show in detail how the peptide backbone and side chains mimic the interactions of the enzyme with chitooligosaccharides. Together with enzymological characterization, the structures explain why argadin shows an order of magnitude stronger inhibition than allosamidin, whereas argifin shows weaker inhibition. The peptides bind to the chitinase in remarkably different ways, which may explain the differences in inhibition constants. The two complexes provide a basis for structure-based design of potent chitinase inhibitors, accessible by standard peptide chemistry. | |||
High-resolution structures of a chitinase complexed with natural product cyclopentapeptide inhibitors: mimicry of carbohydrate substrate.,Houston DR, Shiomi K, Arai N, Omura S, Peter MG, Turberg A, Synstad B, Eijsink VG, van Aalten DM Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9127-32. Epub 2002 Jul 1. PMID:12093900<ref>PMID:12093900</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[ | <div class="pdbe-citations 1h0g" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
==See Also== | |||
*[[Chitinase 3D structures|Chitinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Serratia marcescens]] | [[Category: Serratia marcescens]] | ||
[[Category: Aalten | [[Category: Aalten DMF]] | ||
[[Category: Arai | [[Category: Arai N]] | ||
[[Category: Eijsink | [[Category: Eijsink VGH]] | ||
[[Category: Houston | [[Category: Houston D]] | ||
[[Category: Omura | [[Category: Omura S]] | ||
[[Category: Peter | [[Category: Peter MG]] | ||
[[Category: Shiomi | [[Category: Shiomi K]] | ||
[[Category: Synstad | [[Category: Synstad B]] | ||
[[Category: Turberg | [[Category: Turberg A]] | ||
Latest revision as of 10:51, 15 November 2023
Complex of a chitinase with the natural product cyclopentapeptide argadin from ClonostachysComplex of a chitinase with the natural product cyclopentapeptide argadin from Clonostachys
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 PubMedOver the past years, family 18 chitinases have been validated as potential targets for the design of drugs against human pathogens that contain or interact with chitin during their normal life cycles. Thus far, only one potent chitinase inhibitor has been described in detail, the pseudotrisaccharide allosamidin. Recently, however, two potent natural-product cyclopentapeptide chitinase inhibitors, argifin and argadin, were reported. Here, we describe high-resolution crystal structures that reveal the details of the interactions of these cyclopeptides with a family 18 chitinase. The structures are examples of complexes of a carbohydrate-processing enzyme with high-affinity peptide-based inhibitors and show in detail how the peptide backbone and side chains mimic the interactions of the enzyme with chitooligosaccharides. Together with enzymological characterization, the structures explain why argadin shows an order of magnitude stronger inhibition than allosamidin, whereas argifin shows weaker inhibition. The peptides bind to the chitinase in remarkably different ways, which may explain the differences in inhibition constants. The two complexes provide a basis for structure-based design of potent chitinase inhibitors, accessible by standard peptide chemistry. High-resolution structures of a chitinase complexed with natural product cyclopentapeptide inhibitors: mimicry of carbohydrate substrate.,Houston DR, Shiomi K, Arai N, Omura S, Peter MG, Turberg A, Synstad B, Eijsink VG, van Aalten DM Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9127-32. Epub 2002 Jul 1. PMID:12093900[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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