1you

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1you.gif|left|200px]]<br /><applet load="1you" size="350" color="white" frame="true" align="right" spinBox="true"
+
[[Image:1you.gif|left|200px]]
-
caption="1you, resolution 2.30&Aring;" />
+
 
-
'''Crystal structure of the catalytic domain of MMP-13 complexed with a potent pyrimidinetrione inhibitor'''<br />
+
{{Structure
 +
|PDB= 1you |SIZE=350|CAPTION= <scene name='initialview01'>1you</scene>, resolution 2.30&Aring;
 +
|SITE=
 +
|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=PFD:5-(2-ETHOXYETHYL)-5-[4-(4-FLUOROPHENOXY)PHENOXY]PYRIMIDINE-2,4,6(1H,3H,5H)-TRIONE'>PFD</scene>
 +
|ACTIVITY=
 +
|GENE= MMP13 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
 +
}}
 +
 
 +
'''Crystal structure of the catalytic domain of MMP-13 complexed with a potent pyrimidinetrione inhibitor'''
 +
 
==Overview==
==Overview==
Line 7: Line 16:
==About this Structure==
==About this Structure==
-
1YOU 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=ZN:'>ZN</scene>, <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=PFD:'>PFD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YOU OCA].
+
1YOU 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=1YOU OCA].
==Reference==
==Reference==
-
Potent pyrimidinetrione-based inhibitors of MMP-13 with enhanced selectivity over MMP-14., Blagg JA, Noe MC, Wolf-Gouveia LA, Reiter LA, Laird ER, Chang SP, Danley DE, Downs JT, Elliott NC, Eskra JD, Griffiths RJ, Hardink JR, Haugeto AI, Jones CS, Liras JL, Lopresti-Morrow LL, Mitchell PG, Pandit J, Robinson RP, Subramanyam C, Vaughn-Bowser ML, Yocum SA, Bioorg Med Chem Lett. 2005 Apr 1;15(7):1807-10. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15780611 15780611]
+
Potent pyrimidinetrione-based inhibitors of MMP-13 with enhanced selectivity over MMP-14., Blagg JA, Noe MC, Wolf-Gouveia LA, Reiter LA, Laird ER, Chang SP, Danley DE, Downs JT, Elliott NC, Eskra JD, Griffiths RJ, Hardink JR, Haugeto AI, Jones CS, Liras JL, Lopresti-Morrow LL, Mitchell PG, Pandit J, Robinson RP, Subramanyam C, Vaughn-Bowser ML, Yocum SA, Bioorg Med Chem Lett. 2005 Apr 1;15(7):1807-10. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15780611 15780611]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
Line 21: Line 30:
[[Category: metalloprotease]]
[[Category: metalloprotease]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:07:33 2008''
+
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:25:36 2008''

Revision as of 13:25, 20 March 2008

Image:1you.gif


PDB ID 1you

Drag the structure with the mouse to rotate
, resolution 2.30Å
Ligands: , , and
Gene: MMP13 (Homo sapiens)
Coordinates: save as pdb, mmCIF, xml



Crystal structure of the catalytic domain of MMP-13 complexed with a potent pyrimidinetrione inhibitor


Overview

Through the use of computational modeling, a series of pyrimidinetrione-based inhibitors of MMP-13 was designed based on a lead inhibitor identified through file screening. Incorporation of a biaryl ether moiety at the C-5 position of the pyrimidinetrione ring resulted in a dramatic enhancement of MMP-13 potency. Protein crystallography revealed that this moiety binds in the S(1)(') pocket of the enzyme. Optimization of the C-4 substituent of the terminal aromatic ring led to incorporation of selectivity versus MMP-14 (MT-1 MMP). Structure activity relationships of the biaryl ether substituent are presented as is pharmacokinetic data for a compound that meets our in vitro potency and selectivity goals.

About this Structure

1YOU is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Potent pyrimidinetrione-based inhibitors of MMP-13 with enhanced selectivity over MMP-14., Blagg JA, Noe MC, Wolf-Gouveia LA, Reiter LA, Laird ER, Chang SP, Danley DE, Downs JT, Elliott NC, Eskra JD, Griffiths RJ, Hardink JR, Haugeto AI, Jones CS, Liras JL, Lopresti-Morrow LL, Mitchell PG, Pandit J, Robinson RP, Subramanyam C, Vaughn-Bowser ML, Yocum SA, Bioorg Med Chem Lett. 2005 Apr 1;15(7):1807-10. PMID:15780611

Page seeded by OCA on Thu Mar 20 15:25:36 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1you"
Personal tools