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==Serratia marcescens Chitinase B complexed with macrolide inhibitor 31== | ==Serratia marcescens Chitinase B complexed with macrolide inhibitor 31== | ||
<StructureSection load='4z2j' size='340' side='right' caption='[[4z2j]], [[Resolution|resolution]] 2.60Å' scene=''> | <StructureSection load='4z2j' size='340' side='right'caption='[[4z2j]], [[Resolution|resolution]] 2.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4z2j]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Z2J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Z2J FirstGlance]. <br> | <table><tr><td colspan='2'>[[4z2j]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_marcescens"_(bizio_1823)_trevisan_in_de_toni_and_trevisan_1889 "bacillus marcescens" (bizio 1823) trevisan in de toni and trevisan 1889]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Z2J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Z2J FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=M6G:(1R,2R,3R,6R,7S,8S,9R,10R,12R,13S,17S)-3-ETHYL-2,10-DIHYDROXY-2,6,8,10,12,15,15,17-OCTAMETHYL-5-OXO-9-(PROP-2-YN-1-YLOXY)-4,14,16-TRIOXABICYCLO[11.3.1]HEPTADEC-7-YL+{5-[N-(METHYLCARBAMOYL)CARBAMIMIDAMIDO]PENTYL}CARBAMATE'>M6G</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=M6G:(1R,2R,3R,6R,7S,8S,9R,10R,12R,13S,17S)-3-ETHYL-2,10-DIHYDROXY-2,6,8,10,12,15,15,17-OCTAMETHYL-5-OXO-9-(PROP-2-YN-1-YLOXY)-4,14,16-TRIOXABICYCLO[11.3.1]HEPTADEC-7-YL+{5-[N-(METHYLCARBAMOYL)CARBAMIMIDAMIDO]PENTYL}CARBAMATE'>M6G</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3wd0|3wd0]], [[4z2g|4z2g]], [[4z2h|4z2h]], [[4z2i|4z2i]], [[4z2k|4z2k]], [[4z2l|4z2l]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3wd0|3wd0]], [[4z2g|4z2g]], [[4z2h|4z2h]], [[4z2i|4z2i]], [[4z2k|4z2k]], [[4z2l|4z2l]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">chiB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=615 "Bacillus marcescens" (Bizio 1823) Trevisan in de Toni and Trevisan 1889])</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=4z2j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z2j OCA], [http://pdbe.org/4z2j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4z2j RCSB], [http://www.ebi.ac.uk/pdbsum/4z2j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4z2j 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=4z2j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z2j OCA], [http://pdbe.org/4z2j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4z2j RCSB], [http://www.ebi.ac.uk/pdbsum/4z2j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4z2j ProSAT]</span></td></tr> | ||
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==See Also== | ==See Also== | ||
*[[Chitinase|Chitinase]] | *[[Chitinase 3D structures|Chitinase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Chitinase]] | [[Category: Chitinase]] | ||
[[Category: Large Structures]] | |||
[[Category: Maita, N]] | [[Category: Maita, N]] | ||
[[Category: Sugawara, A]] | [[Category: Sugawara, A]] | ||
[[Category: Sunazuka, T]] | [[Category: Sunazuka, T]] | ||
[[Category: Hydrolase-hydrolase inhibitor complex]] | |||
[[Category: Inhibitor]] | [[Category: Inhibitor]] | ||
[[Category: Macrolide]] | [[Category: Macrolide]] | ||
Revision as of 10:32, 19 June 2019
Serratia marcescens Chitinase B complexed with macrolide inhibitor 31Serratia marcescens Chitinase B complexed with macrolide inhibitor 31
Structural highlights
Publication Abstract from PubMedArgifin, a 17-membered pentapeptide, inhibits chitinase. As argifin has properties that render it unsuitable as a drug development candidate, we devised a mechanism to create the structural component of argifin that bestows the chitinase inhibition and introduce it into a 14-membered macrolide scaffold. Here we describe (1) the designed macrolide, which exhibits approximately 200-fold more potent chitinase inhibition than argifin, (2) the binding modes of the macrolide with Serratia marcescens chitinase B, and (3) the computed analysis explaining the reason for derivatives displaying increased inhibition compared to argifin, the macrolide aglycone displaying inhibition in a nanomolar range. This promises a class of chitinase inhibitors with novel skeletons, providing innovative insight for drug design and the use of macrolides as adaptable, flexible templates for use in drug discovery research and development. Creation of Customized Bioactivity within a 14-Membered Macrolide Scaffold: Design, Synthesis, and Biological Evaluation Using a Family-18 Chitinase.,Sugawara A, Maita N, Gouda H, Yamamoto T, Hirose T, Kimura S, Saito Y, Nakano H, Kasai T, Nakano H, Shiomi K, Hirono S, Watanabe T, Taniguchi H, Omura S, Sunazuka T J Med Chem. 2015 Jun 25;58(12):4984-4997. Epub 2015 Jun 12. PMID:26030312[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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