1waw: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| (17 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
== | ==Specificity and affinity of natural product cyclopentapeptide inhibitor Argadin against human chitinase== | ||
Family 18 chitinases play key roles in organisms ranging from bacteria to | <StructureSection load='1waw' size='340' side='right'caption='[[1waw]], [[Resolution|resolution]] 1.75Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1waw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Clonostachys Clonostachys] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WAW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WAW 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]] 1.75Å</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=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1waw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1waw OCA], [https://pdbe.org/1waw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1waw RCSB], [https://www.ebi.ac.uk/pdbsum/1waw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1waw ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CHIT1_HUMAN CHIT1_HUMAN] Degrades chitin, chitotriose and chitobiose. May participate in the defense against nematodes and other pathogens. Isoform 3 has no enzymatic activity.<ref>PMID:7592832</ref> <ref>PMID:7836450</ref> <ref>PMID:9748235</ref> | |||
== 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/wa/1waw_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=1waw 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> | |||
[[Category: | <div class="pdbe-citations 1waw" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Chitinase 3D structures|Chitinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Clonostachys]] | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Adams DJ]] | |||
[[Category: Adams | [[Category: Aerts JMFG]] | ||
[[Category: Aerts | [[Category: Boot RG]] | ||
[[Category: Boot | [[Category: Hodkinson M]] | ||
[[Category: Hodkinson | [[Category: Houston DR]] | ||
[[Category: Houston | [[Category: Omura S]] | ||
[[Category: Omura | [[Category: Rao FV]] | ||
[[Category: Rao | [[Category: Shiomi K]] | ||
[[Category: Shiomi | [[Category: Van Aalten DMF]] | ||
[[Category: | |||
Latest revision as of 11:08, 15 November 2023
Specificity and affinity of natural product cyclopentapeptide inhibitor Argadin against human chitinaseSpecificity and affinity of natural product cyclopentapeptide inhibitor Argadin against human chitinase
Structural highlights
FunctionCHIT1_HUMAN Degrades chitin, chitotriose and chitobiose. May participate in the defense against nematodes and other pathogens. Isoform 3 has no enzymatic activity.[1] [2] [3] 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[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||