3kc0

From Proteopedia

(Difference between revisions)

Revision as of 08:44, 7 February 2016

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

Structural highlights

3kc0 is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3kbz, 3kc1
Activity:	Fructose-bisphosphatase, with EC number 3.1.3.11
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

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]

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

1 Structural highlights
2 Disease
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3kc0"

@@ Line 2: / Line 2: @@
 <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 [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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KC0 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3kc0]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KC0 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2T5:[(8H-INDENO[1,2-D][1,3]THIAZOL-4-YLOXY)METHYL]PHOSPHONIC+ACID'>2T5</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3kbz|3kbz]], [[3kc1|3kc1]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Fructose-bisphosphatase Fructose-bisphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.11 3.1.3.11] </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=3kc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kc0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3kc0 RCSB], [http://www.ebi.ac.uk/pdbsum/3kc0 PDBsum]</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=3kc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kc0 OCA], [http://pdbe.org/3kc0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kc0 RCSB], [http://www.ebi.ac.uk/pdbsum/3kc0 PDBsum]</span></td></tr>
 </table>
 == Disease ==
@@ Line 18: / Line 18: @@
     <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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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;">
@@ Line 28: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3kc0" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 36: / Line 37: @@
 </StructureSection>
 [[Category: Fructose-bisphosphatase]]
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Hanzawa, H]]
 [[Category: Sone, J]]

3kc0

From Proteopedia

Revision as of 08:44, 7 February 2016

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

Structural highlights

Disease

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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