3rm8: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[ | ==AMCase in complex with Compound 2== | ||
<StructureSection load='3rm8' size='340' side='right' caption='[[3rm8]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3rm8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RM8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RM8 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RM8:2-METHYL-3-{[4-(PYRIDIN-2-YL)PIPERAZIN-1-YL]METHYL}-1H-INDOLE'>RM8</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3rm4|3rm4]], [[3rm9|3rm9]], [[3rme|3rme]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CHIA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3rm8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rm8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3rm8 RCSB], [http://www.ebi.ac.uk/pdbsum/3rm8 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Acidic mammalian chitinase (AMCase) is a member of the glycosyl hydrolase 18 family (EC 3.2.1.14) that has been implicated in the pathophysiology of allergic airway disease such as asthma. Small molecule inhibitors of AMCase were identified using a combination of high-throughput screening, fragment screening, and virtual screening techniques and characterized by enzyme inhibition and NMR and Biacore binding experiments. X-ray structures of the inhibitors in complex with AMCase revealed that the larger more potent HTS hits, e.g. 5-(4-(2-(4-bromophenoxy)ethyl)piperazine-1-yl)-1H-1,2,4-triazol-3-amine 1, spanned from the active site pocket to a hydrophobic pocket. Smaller fragments identified by FBS occupy both these pockets independently and suggest potential strategies for linking fragments. Compound 1 is a 200 nM AMCase inhibitor which reduced AMCase enzymatic activity in the bronchoalveolar lavage fluid in allergen-challenged mice after oral dosing. | |||
Identification and characterization of acidic mammalian chitinase inhibitors.,Cole DC, Olland AM, Jacob J, Brooks J, Bursavich MG, Czerwinski R, DeClercq C, Johnson M, Joseph-McCarthy D, Ellingboe JW, Lin L, Nowak P, Presman E, Strand J, Tam A, Williams CM, Yao S, Tsao DH, Fitz LJ J Med Chem. 2010 Aug 26;53(16):6122-8. PMID:20666458<ref>PMID:20666458</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Chitinase|Chitinase]] | *[[Chitinase|Chitinase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Chitinase]] | [[Category: Chitinase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Olland, A | [[Category: Olland, A]] | ||
[[Category: Hydrolase-hydrolase inhibitor complex]] | [[Category: Hydrolase-hydrolase inhibitor complex]] | ||
Revision as of 15:16, 9 December 2014
AMCase in complex with Compound 2AMCase in complex with Compound 2
Structural highlights
Publication Abstract from PubMedAcidic mammalian chitinase (AMCase) is a member of the glycosyl hydrolase 18 family (EC 3.2.1.14) that has been implicated in the pathophysiology of allergic airway disease such as asthma. Small molecule inhibitors of AMCase were identified using a combination of high-throughput screening, fragment screening, and virtual screening techniques and characterized by enzyme inhibition and NMR and Biacore binding experiments. X-ray structures of the inhibitors in complex with AMCase revealed that the larger more potent HTS hits, e.g. 5-(4-(2-(4-bromophenoxy)ethyl)piperazine-1-yl)-1H-1,2,4-triazol-3-amine 1, spanned from the active site pocket to a hydrophobic pocket. Smaller fragments identified by FBS occupy both these pockets independently and suggest potential strategies for linking fragments. Compound 1 is a 200 nM AMCase inhibitor which reduced AMCase enzymatic activity in the bronchoalveolar lavage fluid in allergen-challenged mice after oral dosing. Identification and characterization of acidic mammalian chitinase inhibitors.,Cole DC, Olland AM, Jacob J, Brooks J, Bursavich MG, Czerwinski R, DeClercq C, Johnson M, Joseph-McCarthy D, Ellingboe JW, Lin L, Nowak P, Presman E, Strand J, Tam A, Williams CM, Yao S, Tsao DH, Fitz LJ J Med Chem. 2010 Aug 26;53(16):6122-8. PMID:20666458[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||||||