3as3

Crystal Structure Analysis of Chitinase A from Vibrio harveyi with novel inhibitors - W275G mutant complex structure with 2-(imidazolin-2-yl)-5-isothiocyanatobenzofuranCrystal Structure Analysis of Chitinase A from Vibrio harveyi with novel inhibitors - W275G mutant complex structure with 2-(imidazolin-2-yl)-5-isothiocyanatobenzofuran

Structural highlights 3as3 is a 1 chain structure with sequence from "achromobacter_harveyi"_johnson_and_shunk_1936 "achromobacter harveyi" johnson and shunk 1936. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , Related: 3aro, 3arp, 3arq, 3arr, 3ars, 3art, 3aru, 3arv, 3arw, 3arx, 3ary, 3arz, 3as0, 3as1, 3as2 Gene: CHIA ("Achromobacter harveyi" Johnson and Shunk 1936) Activity: Chitinase, with EC number 3.2.1.14 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Six novel inhibitors of Vibrio harveyi chitinase A (VhChiA), a family-18 chitinase homolog, were identified by in vitro screening of a library of pharmacologically active compounds. Unlike the previously identified inhibitors that mimicked the reaction intermediates, crystallographic evidence from 14 VhChiA-inhibitor complexes showed that all of the inhibitor molecules occupied the outer part of the substrate-binding cleft at two hydrophobic areas. The interactions at the aglycone location are well defined and tightly associated with Trp-397 and Trp-275, whereas the interactions at the glycone location are patchy, indicating lower affinity and a loose interaction with two consensus residues, Trp-168 and Val-205. When Trp-275 was substituted with glycine (W275G), the binding affinity toward all of the inhibitors dramatically decreased, and in most structures two inhibitor molecules were found to stack against Trp-397 at the aglycone site. Such results indicate that hydrophobic interactions are important for binding of the newly identified inhibitors by the chitinase. X-ray data and isothermal microcalorimetry showed that the inhibitors occupied the active site of VhChiA in three different binding modes, including single-site binding, independent two-site binding, and sequential two-site binding. The inhibitory effect of dequalinium in the low nanomolar range makes this compound an extremely attractive lead compound for plausible development of therapeutics against human diseases involving chitinase-mediated pathologies. Potent family-18 chitinase inhibitors: x-ray structures, affinities, and binding mechanisms.,Pantoom S, Vetter IR, Prinz H, Suginta W J Biol Chem. 2011 Jul 8;286(27):24312-23. Epub 2011 Apr 29. PMID:21531720 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Chitinase 3D structures

spinqualitylabelsall models 3as3, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image