2ath

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[[Image:2ath.gif|left|200px]]<br /><applet load="2ath" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:2ath.gif|left|200px]]
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caption="2ath, resolution 2.28&Aring;" />
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'''Crystal structure of the ligand binding domain of human PPAR-gamma im complex with an agonist'''<br />
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{{Structure
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|PDB= 2ath |SIZE=350|CAPTION= <scene name='initialview01'>2ath</scene>, resolution 2.28&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=3EA:2-{5-[3-(7-PROPYL-3-TRIFLUOROMETHYLBENZO[D]ISOXAZOL-6-YLOXY)PROPOXY]INDOL-1-YL}ETHANOIC ACID'>3EA</scene>
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|ACTIVITY=
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|GENE=
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}}
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'''Crystal structure of the ligand binding domain of human PPAR-gamma im complex with an agonist'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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2ATH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=3EA:'>3EA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ATH OCA].
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2ATH is a [[Single protein]] structure of 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=2ATH OCA].
==Reference==
==Reference==
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Novel indole-based peroxisome proliferator-activated receptor agonists: design, SAR, structural biology, and biological activities., Mahindroo N, Huang CF, Peng YH, Wang CC, Liao CC, Lien TW, Chittimalla SK, Huang WJ, Chai CH, Prakash E, Chen CP, Hsu TA, Peng CH, Lu IL, Lee LH, Chang YW, Chen WC, Chou YC, Chen CT, Goparaju CM, Chen YS, Lan SJ, Yu MC, Chen X, Chao YS, Wu SY, Hsieh HP, J Med Chem. 2005 Dec 29;48(26):8194-208. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16366601 16366601]
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Novel indole-based peroxisome proliferator-activated receptor agonists: design, SAR, structural biology, and biological activities., Mahindroo N, Huang CF, Peng YH, Wang CC, Liao CC, Lien TW, Chittimalla SK, Huang WJ, Chai CH, Prakash E, Chen CP, Hsu TA, Peng CH, Lu IL, Lee LH, Chang YW, Chen WC, Chou YC, Chen CT, Goparaju CM, Chen YS, Lan SJ, Yu MC, Chen X, Chao YS, Wu SY, Hsieh HP, J Med Chem. 2005 Dec 29;48(26):8194-208. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16366601 16366601]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: ppar]]
[[Category: ppar]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:30:50 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:53:44 2008''

Revision as of 13:53, 20 March 2008

Image:2ath.gif


PDB ID 2ath

Drag the structure with the mouse to rotate
, resolution 2.28Å
Ligands:
Coordinates: save as pdb, mmCIF, xml



Crystal structure of the ligand binding domain of human PPAR-gamma im complex with an agonist


Contents

Overview

The synthesis and structure-activity relationship studies of novel indole derivatives as peroxisome proliferator-activated receptor (PPAR) agonists are reported. Indole, a drug-like scaffold, was studied as a core skeleton for the acidic head part of PPAR agonists. The structural features (acidic head, substitution on indole, and linker) were optimized first, by keeping benzisoxazole as the tail part, based on binding and functional activity at PPARgamma protein. The variations in the tail part, by introducing various heteroaromatic ring systems, were then studied. In vitro evaluation led to identification of a novel series of indole compounds with a benzisoxazole tail as potent PPAR agonists with the lead compound 14 (BPR1H036) displaying an excellent pharmacokinetic profile in BALB/c mice and an efficacious glucose lowering activity in KKA(y) mice. Structural biology studies of 14 showed that the indole ring contributes strong hydrophobic interactions with PPARgamma and could be an important moiety for the binding to the protein.

Disease

Known diseases associated with this structure: Abdominal body fat distribution, modifier of OMIM:[601487], Diabetes mellitus, insulin-resistant, with acanthosis nigricans and hypertension OMIM:[601487], Glioblastoma, susceptibility to OMIM:[601487], Insulin resistance, severe, digenic OMIM:[601487], Lipodystrophy, familial partial OMIM:[601487], Obesity, resistance to OMIM:[601487], Obesity, severe OMIM:[601487]

About this Structure

2ATH is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Novel indole-based peroxisome proliferator-activated receptor agonists: design, SAR, structural biology, and biological activities., Mahindroo N, Huang CF, Peng YH, Wang CC, Liao CC, Lien TW, Chittimalla SK, Huang WJ, Chai CH, Prakash E, Chen CP, Hsu TA, Peng CH, Lu IL, Lee LH, Chang YW, Chen WC, Chou YC, Chen CT, Goparaju CM, Chen YS, Lan SJ, Yu MC, Chen X, Chao YS, Wu SY, Hsieh HP, J Med Chem. 2005 Dec 29;48(26):8194-208. PMID:16366601

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