4ayk: Difference between revisions
New page: left|200px<br /> <applet load="4ayk" size="450" color="white" frame="true" align="right" spinBox="true" caption="4ayk" /> '''CATALYTIC FRAGMENT OF HUMAN FIBROBLAST COLL... |
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'''CATALYTIC FRAGMENT OF HUMAN FIBROBLAST COLLAGENASE COMPLEXED WITH CGS-27023A, NMR, 30 STRUCTURES'''<br /> | '''CATALYTIC FRAGMENT OF HUMAN FIBROBLAST COLLAGENASE COMPLEXED WITH CGS-27023A, NMR, 30 STRUCTURES'''<br /> | ||
==Overview== | ==Overview== | ||
The solution structure of the catalytic fragment of human fibroblast | The solution structure of the catalytic fragment of human fibroblast collagenase (MMP-1) complexed with a sulfonamide derivative of a hydroxamic acid compound (CGS-27023A) has been determined using two-dimensional and three-dimensional heteronuclear NMR spectroscopy. The solution structure of the complex was calculated by means of hybrid distance geometry-simulated annealing using a combination of experimental NMR restraints obtained from the previous refinement of the inhibitor-free MMP-1 (1) and recent restraints for the MMP-1:CGS-27023A complex. The hydroxamic acid moiety of CGS-27023A was found to chelate to the "right" of the catalytic zinc where the p-methoxyphenyl sits in the S1' active-site pocket, the isopropyl group is in contact with H83 and N80, and the pyridine ring is solvent exposed. The sulfonyl oxygens are in hydrogen-bonding distance to the backbone NHs of L81 and A82. This is similar to the conformation determined by NMR of the inhibitor bound to stromelysin (2, 3). A total of 48 distance restraints were observed between MMP-1 and CGS-27023A from 3D 13C-edited/12C-filtered NOESY and 3D 15N-edited NOESY experiments. An additional 18 intramolecular restraints were observed for CGS-27023A from a 2D 12C-filtered NOESY experiment. A minimal set of NMR experiments in combination with the free MMP-1 assignments were used to assign the MMP-1 (1)H, 13C, and 15N resonances in the MMP-1:CGS-27023A complex. The assignments of CGS-27023A in the complex were obtained from 2D 12C-filtered NOESY and 2D 12C-filtered TOCSY experiments. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
4AYK 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 ZN, CA and CGS as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Interstitial_collagenase Interstitial collagenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.7 3.4.24.7] Full crystallographic information is available from [http:// | 4AYK 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> and <scene name='pdbligand=CGS:'>CGS</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Interstitial_collagenase Interstitial collagenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.7 3.4.24.7] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AYK OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Interstitial collagenase]] | [[Category: Interstitial collagenase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Moy, F | [[Category: Moy, F J.]] | ||
[[Category: Powers, R.]] | [[Category: Powers, R.]] | ||
[[Category: CA]] | [[Category: CA]] | ||
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[[Category: metalloprotease]] | [[Category: metalloprotease]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:12:48 2008'' | ||
Revision as of 20:12, 21 February 2008
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CATALYTIC FRAGMENT OF HUMAN FIBROBLAST COLLAGENASE COMPLEXED WITH CGS-27023A, NMR, 30 STRUCTURES
OverviewOverview
The solution structure of the catalytic fragment of human fibroblast collagenase (MMP-1) complexed with a sulfonamide derivative of a hydroxamic acid compound (CGS-27023A) has been determined using two-dimensional and three-dimensional heteronuclear NMR spectroscopy. The solution structure of the complex was calculated by means of hybrid distance geometry-simulated annealing using a combination of experimental NMR restraints obtained from the previous refinement of the inhibitor-free MMP-1 (1) and recent restraints for the MMP-1:CGS-27023A complex. The hydroxamic acid moiety of CGS-27023A was found to chelate to the "right" of the catalytic zinc where the p-methoxyphenyl sits in the S1' active-site pocket, the isopropyl group is in contact with H83 and N80, and the pyridine ring is solvent exposed. The sulfonyl oxygens are in hydrogen-bonding distance to the backbone NHs of L81 and A82. This is similar to the conformation determined by NMR of the inhibitor bound to stromelysin (2, 3). A total of 48 distance restraints were observed between MMP-1 and CGS-27023A from 3D 13C-edited/12C-filtered NOESY and 3D 15N-edited NOESY experiments. An additional 18 intramolecular restraints were observed for CGS-27023A from a 2D 12C-filtered NOESY experiment. A minimal set of NMR experiments in combination with the free MMP-1 assignments were used to assign the MMP-1 (1)H, 13C, and 15N resonances in the MMP-1:CGS-27023A complex. The assignments of CGS-27023A in the complex were obtained from 2D 12C-filtered NOESY and 2D 12C-filtered TOCSY experiments.
DiseaseDisease
Known diseases associated with this structure: COPD, rate of decline of lung function in OMIM:[120353]
About this StructureAbout this Structure
4AYK is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Interstitial collagenase, with EC number 3.4.24.7 Full crystallographic information is available from OCA.
ReferenceReference
NMR solution structure of the catalytic fragment of human fibroblast collagenase complexed with a sulfonamide derivative of a hydroxamic acid compound., Moy FJ, Chanda PK, Chen JM, Cosmi S, Edris W, Skotnicki JS, Wilhelm J, Powers R, Biochemistry. 1999 Jun 1;38(22):7085-96. PMID:10353819
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