1w9u

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[[Image:1w9u.jpg|left|200px]]<br /><applet load="1w9u" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1w9u, resolution 1.85&Aring;" />
 
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'''SPECIFICITY AND AFFNITY OF NATURAL PRODUCT CYCLOPENTAPEPTIDE INHIBITOR ARGADIN AGAINST ASPERGILLUS FUMIGATUS CHITINASE'''<br />
 
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==Overview==
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==Specificity and affnity of natural product cyclopentapeptide inhibitor Argadin against Aspergillus fumigatus chitinase==
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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.
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<StructureSection load='1w9u' size='340' side='right'caption='[[1w9u]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1w9u]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_fumigatus Aspergillus fumigatus] and [https://en.wikipedia.org/wiki/Clonostachys Clonostachys]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W9U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W9U FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85&#8491;</td></tr>
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<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=HSE:L-HOMOSERINE'>HSE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UN1:2-AMINOHEXANEDIOIC+ACID'>UN1</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1w9u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w9u OCA], [https://pdbe.org/1w9u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w9u RCSB], [https://www.ebi.ac.uk/pdbsum/1w9u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w9u ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/w9/1w9u_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1w9u ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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==About this Structure==
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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>
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1W9U is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Aspergillus_fumigatus Aspergillus fumigatus] with SO4 and RIG as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Chitinase Chitinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.14 3.2.1.14] Known structural/functional Site: <scene name='pdbsite=AC1:So4 Binding Site For Chain A'>AC1</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1W9U OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15664516 15664516]
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</div>
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[[Category: Aspergillus fumigatus]]
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<div class="pdbe-citations 1w9u" style="background-color:#fffaf0;"></div>
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[[Category: Chitinase]]
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[[Category: Single protein]]
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[[Category: Aalten, D.M.F.Van.]]
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[[Category: Adams, D.J.]]
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[[Category: Aerts, J.M.F.G.]]
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[[Category: Boot, R.G.]]
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[[Category: Hodkinson, M.]]
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[[Category: Houston, D.R.]]
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[[Category: Omura, S.]]
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[[Category: Rao, F.V.]]
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[[Category: Shiomi, K.]]
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[[Category: RIG]]
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[[Category: SO4]]
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[[Category: argadin]]
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[[Category: chitinase]]
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[[Category: chitinase inhibitors]]
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[[Category: cyclopentapeptide inhibitors]]
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[[Category: glycosidase]]
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[[Category: hydrolase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 18:35:40 2007''
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==See Also==
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*[[Chitinase 3D structures|Chitinase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Aspergillus fumigatus]]
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[[Category: Clonostachys]]
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[[Category: Large Structures]]
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[[Category: Adams DJ]]
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[[Category: Aerts JMFG]]
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[[Category: Boot RG]]
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[[Category: Hodkinson M]]
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[[Category: Houston DR]]
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[[Category: Omura S]]
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[[Category: Rao FV]]
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[[Category: Shiomi K]]
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[[Category: Van Aalten DMF]]

Current revision

Specificity and affnity of natural product cyclopentapeptide inhibitor Argadin against Aspergillus fumigatus chitinase

PDB ID 1w9u

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