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New page: left|200px<br /><applet load="1ll4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ll4, resolution 2.8Å" /> '''STRUCTURE OF C. IMMIT... |
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== | ==STRUCTURE OF C. IMMITIS CHITINASE 1 COMPLEXED WITH ALLOSAMIDIN== | ||
Allosamidin is a known inhibitor of class 18 chitinases. We show that | <StructureSection load='1ll4' size='340' side='right'caption='[[1ll4]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1ll4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Coccidioides_immitis Coccidioides immitis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LL4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LL4 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]] 2.8Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMI:ALLOSAMIZOLINE'>AMI</scene>, <scene name='pdbligand=NAA:N-ACETYL-D-ALLOSAMINE'>NAA</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=1ll4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ll4 OCA], [https://pdbe.org/1ll4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ll4 RCSB], [https://www.ebi.ac.uk/pdbsum/1ll4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ll4 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CHI1_COCPS CHI1_COCPS] | |||
== 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/ll/1ll4_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=1ll4 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Allosamidin is a known inhibitor of class 18 chitinases. We show that allosamidin is a competitive inhibitor of the fungal chitinase CiX1 from Coccidioides immitis, with a K(i) of 60 nM. We report the X-ray structure of the complex and show that upon inhibitor binding the side-chain of Asp169 rotates to form an ion pair with the oxazolinium cation. The mechanism of action is thought to involve protonation of the leaving group by Glu171 and substrate assistance by the sugar acetamido moiety to form an oxazoline-like intermediate. We converted both amino acid residues to the corresponding amide and found that each mutation effectively abolishes enzyme activity. X-ray structures show the mutant enzymes retain the basic wild-type structure and that the loss of mutant activity is due to their altered chemical properties. The high affinity of allosamidin, and its similarity to the putative reaction intermediate, suggests it is a transition state analog. This helps validate our contention that the role of Asp169 is to electrostatically stabilize the reaction transition state. | |||
The structure of an allosamidin complex with the Coccidioides immitis chitinase defines a role for a second acid residue in substrate-assisted mechanism.,Bortone K, Monzingo AF, Ernst S, Robertus JD J Mol Biol. 2002 Jul 5;320(2):293-302. PMID:12079386<ref>PMID:12079386</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[ | <div class="pdbe-citations 1ll4" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Chitinase 3D structures|Chitinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Coccidioides immitis]] | [[Category: Coccidioides immitis]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Bortone | [[Category: Bortone K]] | ||
[[Category: Ernst | [[Category: Ernst S]] | ||
[[Category: Monzingo | [[Category: Monzingo AF]] | ||
[[Category: Robertus | [[Category: Robertus JD]] | ||
Latest revision as of 12:15, 16 August 2023
STRUCTURE OF C. IMMITIS CHITINASE 1 COMPLEXED WITH ALLOSAMIDINSTRUCTURE OF C. IMMITIS CHITINASE 1 COMPLEXED WITH ALLOSAMIDIN
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 PubMedAllosamidin is a known inhibitor of class 18 chitinases. We show that allosamidin is a competitive inhibitor of the fungal chitinase CiX1 from Coccidioides immitis, with a K(i) of 60 nM. We report the X-ray structure of the complex and show that upon inhibitor binding the side-chain of Asp169 rotates to form an ion pair with the oxazolinium cation. The mechanism of action is thought to involve protonation of the leaving group by Glu171 and substrate assistance by the sugar acetamido moiety to form an oxazoline-like intermediate. We converted both amino acid residues to the corresponding amide and found that each mutation effectively abolishes enzyme activity. X-ray structures show the mutant enzymes retain the basic wild-type structure and that the loss of mutant activity is due to their altered chemical properties. The high affinity of allosamidin, and its similarity to the putative reaction intermediate, suggests it is a transition state analog. This helps validate our contention that the role of Asp169 is to electrostatically stabilize the reaction transition state. The structure of an allosamidin complex with the Coccidioides immitis chitinase defines a role for a second acid residue in substrate-assisted mechanism.,Bortone K, Monzingo AF, Ernst S, Robertus JD J Mol Biol. 2002 Jul 5;320(2):293-302. PMID:12079386[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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