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== | ==Specificity and affinity of natural product cyclopentapeptide inhibitors against Aspergillus fumigatus, human and bacterial chitinaseFra== | ||
Family 18 chitinases play key roles in organisms ranging from bacteria to | <StructureSection load='1w9p' size='340' side='right'caption='[[1w9p]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1w9p]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_fumigatus Aspergillus fumigatus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W9P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W9P 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]] 1.7Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=1w9p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w9p OCA], [https://pdbe.org/1w9p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w9p RCSB], [https://www.ebi.ac.uk/pdbsum/1w9p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w9p ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CHIB1_ASPFM CHIB1_ASPFM] Major secreted chitinase involved in the degradation of chitin, a component of the cell walls of fungi and exoskeletal elements of some animals (including worms and arthropods). Plays a role in the morphogenesis and autolysis (By similarity). | |||
== 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/w9/1w9p_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=1w9p ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Family 18 chitinases play key roles in organisms ranging from bacteria to man. There is a need for specific, potent inhibitors to probe the function of these chitinases in different organisms. Such molecules could also provide leads for the development of chemotherapeuticals with fungicidal, insecticidal, or anti-inflammatory potential. Recently, two natural product peptides, argifin and argadin, have been characterized, which structurally mimic chitinase-chitooligosaccharide interactions and inhibit a bacterial chitinase in the nM-mM range. Here, we show that these inhibitors also act on human and Aspergillus fumigatus chitinases. The structures of these enzymes in complex with argifin and argadin, together with mutagenesis, fluorescence, and enzymology, reveal that subtle changes in the binding site dramatically affect affinity and selectivity. The data show that it may be possible to develop specific chitinase inhibitors based on the argifin/argadin scaffolds. | |||
Specificity and affinity of natural product cyclopentapeptide inhibitors against A. fumigatus, human, and bacterial chitinases.,Rao FV, Houston DR, Boot RG, Aerts JM, Hodkinson M, Adams DJ, Shiomi K, Omura S, van Aalten DM Chem Biol. 2005 Jan;12(1):65-76. PMID:15664516<ref>PMID:15664516</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1w9p" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Chitinase 3D structures|Chitinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Aspergillus fumigatus]] | [[Category: Aspergillus fumigatus]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Adams DJ]] | |||
[[Category: Aerts JMFG]] | |||
[[Category: Adams | [[Category: Boot RG]] | ||
[[Category: Aerts | [[Category: Hodkinson M]] | ||
[[Category: Boot | [[Category: Houston DR]] | ||
[[Category: Hodkinson | [[Category: Omura S]] | ||
[[Category: Houston | [[Category: Rao FV]] | ||
[[Category: Omura | [[Category: Shiomi K]] | ||
[[Category: Rao | [[Category: Van Aalten DMF]] | ||
[[Category: Shiomi | |||
[[Category: | |||
Latest revision as of 16:24, 13 December 2023
Specificity and affinity of natural product cyclopentapeptide inhibitors against Aspergillus fumigatus, human and bacterial chitinaseFraSpecificity and affinity of natural product cyclopentapeptide inhibitors against Aspergillus fumigatus, human and bacterial chitinaseFra
Structural highlights
FunctionCHIB1_ASPFM Major secreted chitinase involved in the degradation of chitin, a component of the cell walls of fungi and exoskeletal elements of some animals (including worms and arthropods). Plays a role in the morphogenesis and autolysis (By similarity). 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 PubMedFamily 18 chitinases play key roles in organisms ranging from bacteria to man. There is a need for specific, potent inhibitors to probe the function of these chitinases in different organisms. Such molecules could also provide leads for the development of chemotherapeuticals with fungicidal, insecticidal, or anti-inflammatory potential. Recently, two natural product peptides, argifin and argadin, have been characterized, which structurally mimic chitinase-chitooligosaccharide interactions and inhibit a bacterial chitinase in the nM-mM range. Here, we show that these inhibitors also act on human and Aspergillus fumigatus chitinases. The structures of these enzymes in complex with argifin and argadin, together with mutagenesis, fluorescence, and enzymology, reveal that subtle changes in the binding site dramatically affect affinity and selectivity. The data show that it may be possible to develop specific chitinase inhibitors based on the argifin/argadin scaffolds. Specificity and affinity of natural product cyclopentapeptide inhibitors against A. fumigatus, human, and bacterial chitinases.,Rao FV, Houston DR, Boot RG, Aerts JM, Hodkinson M, Adams DJ, Shiomi K, Omura S, van Aalten DM Chem Biol. 2005 Jan;12(1):65-76. PMID:15664516[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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