3kc0: Difference between revisions

Latest revision as of 16:10, 1 November 2023

Crystal structure of human liver FBPase in complex with tricyclic inhibitor 10b

Structural highlights

3kc0 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.8Å
Ligands:	2T5
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

F16P1_HUMAN Defects in FBP1 are the cause of fructose-1,6-bisphosphatase deficiency (FBPD) [MIM:229700. FBPD is inherited as an autosomal recessive disorder mainly in the liver and causes life-threatening episodes of hypoglycemia and metabolic acidosis (lactacidemia) in newborn infants or young children.^[1] ^[2]

Function

F16P1_HUMAN

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

With the goal of improving metabolic stability and further enhancing FBPase inhibitory activity, a series of tricyclic 8H-indeno[1,2-d][1,3]thiazoles was designed and synthesized with the aid of structure-based drug design. Extensive SAR studies led to the discovery of 19a with an IC(50) value of 1nM against human FBPase. X-ray crystallographic studies revealed that high affinity of 19a was due to the hydrophobic interaction arising from better shape complementarity and to the hydrogen bonding network involving the side chain on the tricyclic scaffold.

Structure-based drug design of tricyclic 8H-indeno[1,2-d][1,3]thiazoles as potent FBPase inhibitors.,Tsukada T, Takahashi M, Takemoto T, Kanno O, Yamane T, Kawamura S, Nishi T Bioorg Med Chem Lett. 2010 Feb 1;20(3):1004-7. Epub 2009 Dec 21. PMID:20045638^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kikawa Y, Inuzuka M, Jin BY, Kaji S, Koga J, Yamamoto Y, Fujisawa K, Hata I, Nakai A, Shigematsu Y, Mizunuma H, Taketo A, Mayumi M, Sudo M. Identification of genetic mutations in Japanese patients with fructose-1,6-bisphosphatase deficiency. Am J Hum Genet. 1997 Oct;61(4):852-61. PMID:9382095
↑ Matsuura T, Chinen Y, Arashiro R, Katsuren K, Tamura T, Hyakuna N, Ohta T. Two newly identified genomic mutations in a Japanese female patient with fructose-1,6-bisphosphatase (FBPase) deficiency. Mol Genet Metab. 2002 Jul;76(3):207-10. PMID:12126934
↑ Tsukada T, Takahashi M, Takemoto T, Kanno O, Yamane T, Kawamura S, Nishi T. Structure-based drug design of tricyclic 8H-indeno[1,2-d][1,3]thiazoles as potent FBPase inhibitors. Bioorg Med Chem Lett. 2010 Feb 1;20(3):1004-7. Epub 2009 Dec 21. PMID:20045638 doi:10.1016/j.bmcl.2009.12.056

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Kikawa Y, Inuzuka M, Jin BY, Kaji S, Koga J, Yamamoto Y, Fujisawa K, Hata I, Nakai A, Shigematsu Y, Mizunuma H, Taketo A, Mayumi M, Sudo M. Identification of genetic mutations in Japanese patients with fructose-1,6-bisphosphatase deficiency. Am J Hum Genet. 1997 Oct;61(4):852-61. PMID:9382095

[2] Matsuura T, Chinen Y, Arashiro R, Katsuren K, Tamura T, Hyakuna N, Ohta T. Two newly identified genomic mutations in a Japanese female patient with fructose-1,6-bisphosphatase (FBPase) deficiency. Mol Genet Metab. 2002 Jul;76(3):207-10. PMID:12126934

[3] Tsukada T, Takahashi M, Takemoto T, Kanno O, Yamane T, Kawamura S, Nishi T. Structure-based drug design of tricyclic 8H-indeno[1,2-d][1,3]thiazoles as potent FBPase inhibitors. Bioorg Med Chem Lett. 2010 Feb 1;20(3):1004-7. Epub 2009 Dec 21. PMID:20045638 doi:10.1016/j.bmcl.2009.12.056

[1]

[2]

[3]

@@ Line 1: / Line 1: @@
-[[Image:3kc0.png|left|200px]]
-{{STRUCTURE_3kc0|  PDB=3kc0  |  SCENE=  }}
+==Crystal structure of human liver FBPase in complex with tricyclic inhibitor 10b==
+<StructureSection load='3kc0' size='340' side='right'caption='[[3kc0]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3kc0]] is a 4 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=3KC0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KC0 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]] 2.8&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2T5:[(8H-INDENO[1,2-D][1,3]THIAZOL-4-YLOXY)METHYL]PHOSPHONIC+ACID'>2T5</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=3kc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kc0 OCA], [https://pdbe.org/3kc0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kc0 RCSB], [https://www.ebi.ac.uk/pdbsum/3kc0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kc0 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/F16P1_HUMAN F16P1_HUMAN] Defects in FBP1 are the cause of fructose-1,6-bisphosphatase deficiency (FBPD) [MIM:[https://omim.org/entry/229700 229700]. FBPD is inherited as an autosomal recessive disorder mainly in the liver and causes life-threatening episodes of hypoglycemia and metabolic acidosis (lactacidemia) in newborn infants or young children.<ref>PMID:9382095</ref> <ref>PMID:12126934</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/F16P1_HUMAN F16P1_HUMAN]
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kc/3kc0_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3kc0 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+With the goal of improving metabolic stability and further enhancing FBPase inhibitory activity, a series of tricyclic 8H-indeno[1,2-d][1,3]thiazoles was designed and synthesized with the aid of structure-based drug design. Extensive SAR studies led to the discovery of 19a with an IC(50) value of 1nM against human FBPase. X-ray crystallographic studies revealed that high affinity of 19a was due to the hydrophobic interaction arising from better shape complementarity and to the hydrogen bonding network involving the side chain on the tricyclic scaffold.
-===Crystal structure of human liver FBPase in complex with tricyclic inhibitor 10b===
+Structure-based drug design of tricyclic 8H-indeno[1,2-d][1,3]thiazoles as potent FBPase inhibitors.,Tsukada T, Takahashi M, Takemoto T, Kanno O, Yamane T, Kawamura S, Nishi T Bioorg Med Chem Lett. 2010 Feb 1;20(3):1004-7. Epub 2009 Dec 21. PMID:20045638<ref>PMID:20045638</ref>
-{{ABSTRACT_PUBMED_20045638}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 3kc0" style="background-color:#fffaf0;"></div>
-[[3kc0]] is a 4 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=3KC0 OCA].
 ==See Also==
 *[[Fructose-1%2C6-bisphosphatase|Fructose-1%2C6-bisphosphatase]]
+*[[Fructose-1%2C6-bisphosphatase 3D structures|Fructose-1%2C6-bisphosphatase 3D structures]]
-==Reference==
+== References ==
-<ref group="xtra">PMID:020045638</ref><references group="xtra"/>
+<references/>
-[[Category: Fructose-bisphosphatase]]
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Hanzawa, H.]]
+[[Category: Large Structures]]
-[[Category: Sone, J.]]
+[[Category: Hanzawa H]]
-[[Category: Takahashi, M.]]
+[[Category: Sone J]]
-[[Category: Allosteric enzyme]]
+[[Category: Takahashi M]]
-[[Category: Carbohydrate metabolism]]
-[[Category: Disease mutation]]
-[[Category: Gluconeogenesis]]
-[[Category: Hydrolase]]
-[[Category: Magnesium]]
-[[Category: Metal-binding]]

3kc0: Difference between revisions

Latest revision as of 16:10, 1 November 2023

Crystal structure of human liver FBPase in complex with tricyclic inhibitor 10b

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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