2a3c

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[[Image:2a3c.gif|left|200px]]
 
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{{Structure
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==Crystal structure of Aspergillus fumigatus chitinase B1 in complex with pentoxifylline==
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|PDB= 2a3c |SIZE=350|CAPTION= <scene name='initialview01'>2a3c</scene>, resolution 2.07&Aring;
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<StructureSection load='2a3c' size='340' side='right'caption='[[2a3c]], [[Resolution|resolution]] 2.07&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=PNX:3,7-DIMETHYL-1-(5-OXOHEXYL)-3,7-DIHYDRO-1H-PURINE-2,6-DIONE'>PNX</scene>
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<table><tr><td colspan='2'>[[2a3c]] 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=2A3C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2A3C FirstGlance]. <br>
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|ACTIVITY= [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]
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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]] 2.07&#8491;</td></tr>
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|GENE=
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PNX:3,7-DIMETHYL-1-(5-OXOHEXYL)-3,7-DIHYDRO-1H-PURINE-2,6-DIONE'>PNX</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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}}
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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=2a3c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a3c OCA], [https://pdbe.org/2a3c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2a3c RCSB], [https://www.ebi.ac.uk/pdbsum/2a3c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2a3c 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/a3/2a3c_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=2a3c 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 a range of pathogenic organisms and are overexpressed in the asthmatic lung. By screening a library of marketed drug molecules, we have identified methylxanthine derivatives as possible inhibitor leads. These derivatives, theophylline, caffeine, and pentoxifylline, are used therapeutically as antiinflammatory agents, with pleiotropic mechanisms of action. Here it is shown that they are also competitive inhibitors against a fungal family 18 chitinase, with pentoxifylline being the most potent (K(i) of 37 microM). Crystallographic analysis of chitinase-inhibitor complexes revealed specific interactions with the active site, mimicking the reaction intermediate analog, allosamidin. Mutagenesis identified the key active site residues, conserved in mammalian chitinases, which contribute to inhibitor affinity. Enzyme assays also revealed that these methylxanthines are active against human chitinases.
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'''Crystal structure of Aspergillus fumigatus chitinase B1 in complex with pentoxifylline'''
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Methylxanthine drugs are chitinase inhibitors: investigation of inhibition and binding modes.,Rao FV, Andersen OA, Vora KA, Demartino JA, van Aalten DM Chem Biol. 2005 Sep;12(9):973-80. PMID:16183021<ref>PMID:16183021</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2a3c" style="background-color:#fffaf0;"></div>
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==Overview==
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==See Also==
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Family 18 chitinases play key roles in a range of pathogenic organisms and are overexpressed in the asthmatic lung. By screening a library of marketed drug molecules, we have identified methylxanthine derivatives as possible inhibitor leads. These derivatives, theophylline, caffeine, and pentoxifylline, are used therapeutically as antiinflammatory agents, with pleiotropic mechanisms of action. Here it is shown that they are also competitive inhibitors against a fungal family 18 chitinase, with pentoxifylline being the most potent (K(i) of 37 microM). Crystallographic analysis of chitinase-inhibitor complexes revealed specific interactions with the active site, mimicking the reaction intermediate analog, allosamidin. Mutagenesis identified the key active site residues, conserved in mammalian chitinases, which contribute to inhibitor affinity. Enzyme assays also revealed that these methylxanthines are active against human chitinases.
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*[[Chitinase 3D structures|Chitinase 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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2A3C is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Aspergillus_fumigatus Aspergillus fumigatus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A3C OCA].
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__TOC__
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</StructureSection>
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==Reference==
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Methylxanthine drugs are chitinase inhibitors: investigation of inhibition and binding modes., Rao FV, Andersen OA, Vora KA, Demartino JA, van Aalten DM, Chem Biol. 2005 Sep;12(9):973-80. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16183021 16183021]
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[[Category: Aspergillus fumigatus]]
[[Category: Aspergillus fumigatus]]
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[[Category: Chitinase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Andersen OA]]
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[[Category: Aalten, D M.F van.]]
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[[Category: DeMartino JA]]
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[[Category: Andersen, O A.]]
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[[Category: Rao FV]]
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[[Category: DeMartino, J A.]]
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[[Category: Vora KA]]
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[[Category: Rao, F V.]]
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[[Category: Van Aalten DMF]]
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[[Category: Vora, K A.]]
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[[Category: PNX]]
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[[Category: SO4]]
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[[Category: (beta-alpha)8 barrel]]
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[[Category: chitinase-pentoxifylline complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:44:51 2008''
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Current revision

Crystal structure of Aspergillus fumigatus chitinase B1 in complex with pentoxifylline

PDB ID 2a3c

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