OCA at 17:43, 29 November 2023

OCA — Wed, 29 Nov 2023 17:43:41 GMT

←Older revision		Revision as of 17:43, 29 November 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7wqr is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of Aldo-keto reductase 1C3 complexed with compound 28==
		+	<StructureSection load='7wqr' size='340' side='right'caption='[[7wqr]], [[Resolution\|resolution]] 2.12Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7wqr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WQR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WQR 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]] 2.124Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4R6:~{N}-(3-chlorophenyl)-2-[(3,5-dimethyl-1,2-oxazol-4-yl)methoxy]benzamide'>4R6</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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=7wqr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wqr OCA], [https://pdbe.org/7wqr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wqr RCSB], [https://www.ebi.ac.uk/pdbsum/7wqr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wqr ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/AK1C3_HUMAN AK1C3_HUMAN] Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2. Functions as a bi-directional 3-alpha-, 17-beta- and 20-alpha HSD. Can interconvert active androgens, estrogens and progestins with their cognate inactive metabolites. Preferentially transforms androstenedione (4-dione) to testosterone.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Aldo-keto reductase 1C3 (AKR1C3) is overexpressed in multiple hormone related cancers, such as breast and prostate cancer, and is correlated with tumor development and aggressiveness. As a phase I biotransformation enzyme, AKR1C3 catalyzes the metabolic processes that lead to resistance to anthracyclines, the "gold standard" for breast cancer treatment. Novel approaches to restore the chemotherapy sensitivity of breast cancer are urgently required. Herein, we developed a new class of AKR1C3 inhibitors that demonstrated potent inhibitory activity and exquisite selectivity for closely related isoforms. The best derivative 27 (S19-1035) exhibits an IC(50) value of 3.04 nM for AKR1C3 and >3289-fold selectivity over other isoforms. We determined the co-crystal structures of AKR1C3 with three of the inhibitors, providing a solid foundation for further structure-based drug optimization. Co-administration of these AKR1C3 inhibitors significantly reversed the doxorubicin (DOX) resistance in a resistant breast cancer cell line. Therefore, the novel AKR1C3 specific inhibitors developed in this work may serve as effective adjuvants to overcome DOX resistance in breast cancer treatment.

-	~~Authors: Jiang, J~~., Liu, Y~~., He, S.~~, Chen, Y., ~~Chu~~, X~~., Liu, Y.~~, Guo, Q., Zhao, L., Feng, F., Liu, W., Zhang, X., ~~Sun~~, H., Fang, P.	+	Development of highly potent and specific AKR1C3 inhibitors to restore the chemosensitivity of drug-resistant breast cancer.,Liu Y, Chen Y, Jiang J, Chu X, Guo Q, Zhao L, Feng F, Liu W, Zhang X, He S, Yang P, Fang P, Sun H Eur J Med Chem. 2023 Feb 5;247:115013. doi: 10.1016/j.ejmech.2022.115013. Epub , 2022 Dec 13. PMID:36566714<ref>PMID:36566714</ref>

-	~~Description: Crystal structure~~ of ~~Aldo~~-~~keto reductase 1C3 complexed with compound 28~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[~~Category: Unreleased Structures~~]]	+	</div>
-	[[Category: ~~He, S~~]]	+	<div class="pdbe-citations 7wqr" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Liu, W~~]]	+
-	[[Category: ~~Fang, P~~]]	+	==See Also==
-	[[Category: ~~Jiang, J~~]]	+	*[[Prostaglandin F synthase 3D structures\|Prostaglandin F synthase 3D structures]]
-	[[Category: ~~Chen, Y~~]]	+	== References ==
-	[[Category: ~~Zhang, X~~]]	+	<references/>
-	[[Category: Guo, Q]]	+	__TOC__
-	[[Category: ~~Zhao, L~~]]	+	</StructureSection>
-	[[Category: ~~Sun, H~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Feng, F~~]]	+	[[Category: Large Structures]]
-	[[Category: Liu, Y]]	+	[[Category: Chen Y]]
-	[[Category: ~~Chu,~~ X]]	+	[[Category: Chu X]]
		+	[[Category: Fang P]]
		+	[[Category: Feng F]]
		+	[[Category: Guo Q]]
		+	[[Category: He S]]
		+	[[Category: Jiang J]]
		+	[[Category: Liu W]]
		+	[[Category: Liu Y]]
		+	[[Category: Sun H]]
		+	[[Category: Zhang X]]
		+	[[Category: Zhao L]]

OCA at 09:17, 16 February 2022

OCA — Wed, 16 Feb 2022 09:17:51 GMT

←Older revision		Revision as of 09:17, 16 February 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7wqr is ON HOLD	+	The entry 7wqr is ON HOLD until Paper Publication

	Authors: Jiang, J., Liu, Y., He, S., Chen, Y., Chu, X., Liu, Y., Guo, Q., Zhao, L., Feng, F., Liu, W., Zhang, X., Sun, H., Fang, P.		Authors: Jiang, J., Liu, Y., He, S., Chen, Y., Chu, X., Liu, Y., Guo, Q., Zhao, L., Feng, F., Liu, W., Zhang, X., Sun, H., Fang, P.

OCA: Protected "7wqr" [edit=sysop:move=sysop]

OCA — Wed, 02 Feb 2022 05:51:08 GMT

Protected "7wqr" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:51, 2 February 2022

OCA: New page: '''Unreleased structure''' The entry 7wqr is ON HOLD Authors: Jiang, J., Liu, Y., He, S., Chen, Y., Chu, X., Liu, Y., Guo, Q., Zhao, L., Feng, F., Liu, W., Zhang, X., Sun, H., Fang, P. ...

OCA — Wed, 02 Feb 2022 05:51:07 GMT

New page: '''Unreleased structure''' The entry 7wqr is ON HOLD Authors: Jiang, J., Liu, Y., He, S., Chen, Y., Chu, X., Liu, Y., Guo, Q., Zhao, L., Feng, F., Liu, W., Zhang, X., Sun, H., Fang, P. ...

New page

'''Unreleased structure'''

The entry 7wqr is ON HOLD

Authors: Jiang, J., Liu, Y., He, S., Chen, Y., Chu, X., Liu, Y., Guo, Q., Zhao, L., Feng, F., Liu, W., Zhang, X., Sun, H., Fang, P.

Description: Crystal structure of Aldo-keto reductase 1C3 complexed with compound 28
[[Category: Unreleased Structures]]
[[Category: He, S]]
[[Category: Liu, W]]
[[Category: Fang, P]]
[[Category: Jiang, J]]
[[Category: Chen, Y]]
[[Category: Zhang, X]]
[[Category: Guo, Q]]
[[Category: Zhao, L]]
[[Category: Sun, H]]
[[Category: Feng, F]]
[[Category: Liu, Y]]
[[Category: Chu, X]]

7wqr - Revision history

OCA at 17:43, 29 November 2023

OCA at 09:17, 16 February 2022

OCA: Protected "7wqr" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7wqr is ON HOLD Authors: Jiang, J., Liu, Y., He, S., Chen, Y., Chu, X., Liu, Y., Guo, Q., Zhao, L., Feng, F., Liu, W., Zhang, X., Sun, H., Fang, P. ...