4z2g: Difference between revisions
New page: '''Unreleased structure''' The entry 4z2g is ON HOLD Authors: Maita, N., Sugawara, A., Sunazuka, T. Description: Serratia marcescens Chitinase B complexed with macrolide inhibitor 21 [... |
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==Serratia marcescens Chitinase B complexed with macrolide inhibitor 26== | |||
<StructureSection load='4z2g' size='340' side='right'caption='[[4z2g]], [[Resolution|resolution]] 2.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4z2g]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Serratia_marcescens Serratia marcescens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Z2G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Z2G 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]] 2.6Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M6V:(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+{4-[N-(METHYLCARBAMOYL)CARBAMIMIDAMIDO]BUTYL}CARBAMATE'>M6V</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=4z2g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z2g OCA], [https://pdbe.org/4z2g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4z2g RCSB], [https://www.ebi.ac.uk/pdbsum/4z2g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4z2g ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CHIB_SERMA CHIB_SERMA] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Argifin, 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<ref>PMID:26030312</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 4z2g" style="background-color:#fffaf0;"></div> | ||
[[Category: Sugawara | |||
[[Category: | ==See Also== | ||
*[[Chitinase 3D structures|Chitinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Serratia marcescens]] | |||
[[Category: Maita N]] | |||
[[Category: Sugawara A]] | |||
[[Category: Sunazuka T]] | |||
Latest revision as of 18:41, 8 November 2023
Serratia marcescens Chitinase B complexed with macrolide inhibitor 26Serratia marcescens Chitinase B complexed with macrolide inhibitor 26
Structural highlights
FunctionPublication 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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