4wkf: Difference between revisions
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<StructureSection load='4wkf' size='340' side='right' caption='[[4wkf]], [[Resolution|resolution]] 1.10Å' scene=''> | <StructureSection load='4wkf' size='340' side='right' caption='[[4wkf]], [[Resolution|resolution]] 1.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4wkf]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WKF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WKF FirstGlance]. <br> | <table><tr><td colspan='2'>[[4wkf]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WKF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WKF FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CBS:DI(N-ACETYL-D-GLUCOSAMINE)'>CBS</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CBS:DI(N-ACETYL-D-GLUCOSAMINE)'>CBS</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CHIT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4wkf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wkf OCA], [http://pdbe.org/4wkf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4wkf RCSB], [http://www.ebi.ac.uk/pdbsum/4wkf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4wkf ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4wkf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wkf OCA], [http://pdbe.org/4wkf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4wkf RCSB], [http://www.ebi.ac.uk/pdbsum/4wkf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4wkf ProSAT]</span></td></tr> | ||
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</div> | </div> | ||
<div class="pdbe-citations 4wkf" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4wkf" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Chitinase]] | [[Category: Chitinase]] | ||
[[Category: Human]] | |||
[[Category: Cachau, R]] | [[Category: Cachau, R]] | ||
[[Category: Cousido-Siah, A]] | [[Category: Cousido-Siah, A]] | ||
Revision as of 23:23, 24 January 2018
Crystal structure of human chitotriosidase-1 catalytic domain in complex with chitobiose (2.5mM) at 1.10 A resolutionCrystal structure of human chitotriosidase-1 catalytic domain in complex with chitobiose (2.5mM) at 1.10 A resolution
Structural highlights
Function[CHIT1_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] Publication Abstract from PubMedChitotriosidase (CHIT1) is a human chitinase belonging to the highly conserved glycosyl hydrolase family 18 (GH18). GH18 enzymes hydrolyze chitin, an N-acetylglucosamine polymer synthesized by lower organisms for structural purposes. Recently, CHIT1 has attracted attention owing to its upregulation in immune-system disorders and as a marker of Gaucher disease. The 39 kDa catalytic domain shows a conserved cluster of three acidic residues, Glu140, Asp138 and Asp136, involved in the hydrolysis reaction. Under an excess concentration of substrate, CHIT1 and other homologues perform an additional activity, transglycosylation. To understand the catalytic mechanism of GH18 chitinases and the dual enzymatic activity, the structure and mechanism of CHIT1 were analyzed in detail. The resolution of the crystals of the catalytic domain was improved from 1.65 A (PDB entry 1waw) to 0.95-1.10 A for the apo and pseudo-apo forms and the complex with chitobiose, allowing the determination of the protonation states within the active site. This information was extended by hybrid quantum mechanics/molecular mechanics (QM/MM) calculations. The results suggest a new mechanism involving changes in the conformation and protonation state of the catalytic triad, as well as a new role for Tyr27, providing new insights into the hydrolysis and transglycosylation activities. New insights into the enzymatic mechanism of human chitotriosidase (CHIT1) catalytic domain by atomic resolution X-ray diffraction and hybrid QM/MM.,Fadel F, Zhao Y, Cachau R, Cousido-Siah A, Ruiz FX, Harlos K, Howard E, Mitschler A, Podjarny A Acta Crystallogr D Biol Crystallogr. 2015 Jul 1;71(Pt 7):1455-70. doi:, 10.1107/S139900471500783X. Epub 2015 Jun 30. PMID:26143917[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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