1fm1: Difference between revisions

Revision as of 12:10, 20 March 2008

Ligands:

, and

Coordinates:

SOLUTION STRUCTURE OF THE CATALYTIC FRAGMENT OF HUMAN COLLAGENASE-3 (MMP-13) COMPLEXED WITH A HYDROXAMIC ACID INHIBITOR

OverviewOverview

The high-resolution solution structure of the catalytic fragment of human collagenase-3 (MMP-13) complexed with a sulfonamide derivative of a hydroxamic acid compound (WAY-151693) has been determined by multidimensional heteronuclear NMR. A total of 30 structures were calculated for residues 7-164 by means of hybrid distance geometry-simulated annealing using a total of 3280 experimental NMR restraints. The atomic rms distribution about the mean coordinate positions for the 30 structures is 0.43(+/-0.05) A for the backbone atoms, 0.80(+/-0.09) A for all atoms, and 0.47(+/-0.04) A for all atoms excluding disordered side-chains. The overall structure of MMP-13 is composed of a beta-sheet consisting of five beta-strands in a mixed parallel and anti-parallel arrangement and three alpha-helices where its overall fold is consistent with previously solved MMP structures. A comparison of the NMR structure of MMP-13 with the published 1.6 A resolution X-ray structure indicates that the major differences between the structures is associated with loop dynamics and crystal-packing interactions. The side-chains of some active-site residues for the NMR and X-ray structures of MMP-13 adopt distinct conformations. This is attributed to the presence of unique inhibitors in the two structures that encounter distinct interactions with MMP-13. The major structural difference observed between the MMP-13 and MMP-1 NMR structures is the relative size and shape of the S1' pocket where this pocket is significantly longer for MMP-13, nearly reaching the surface of the protein. Additionally, MMP-1 and MMP-13 exhibit different dynamic properties for the active-site loop and the structural Zn-binding region. The inhibitor WAY-151693 is well defined in the MMP-13 active-site based on a total of 52 distance restraints. The binding motif of WAY-151693 in the MMP-13 complex is consistent with our previously reported MMP-1:CGS-27023A NMR structure and is similar to the MMP-13: RS-130830 X-ray structure.

About this StructureAbout this Structure

1FM1 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

High-resolution solution structure of the catalytic fragment of human collagenase-3 (MMP-13) complexed with a hydroxamic acid inhibitor., Moy FJ, Chanda PK, Chen JM, Cosmi S, Edris W, Levin JI, Powers R, J Mol Biol. 2000 Sep 22;302(3):671-89. PMID:10986126

Page seeded by OCA on Thu Mar 20 11:10:57 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:1fm1.gif|left|200px]]<br /><applet load="1fm1" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:1fm1.gif|left|200px]]
-caption="1fm1" />
-'''SOLUTION STRUCTURE OF THE CATALYTIC FRAGMENT OF HUMAN COLLAGENASE-3 (MMP-13) COMPLEXED WITH A HYDROXAMIC ACID INHIBITOR'''<br />
+ {{Structure
+|PDB= 1fm1 |SIZE=350|CAPTION= <scene name='initialview01'>1fm1</scene>
+|SITE=
+|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> and <scene name='pdbligand=WAY:N-HYDROXY-2-[(4-METHOXY-BENZENESULFONYL)-PYRIDIN-3-YLMETHYL-AMINO]-3-METHYL-BENZAMIDE'>WAY</scene>
+|ACTIVITY=
+|GENE=
+}}
+'''SOLUTION STRUCTURE OF THE CATALYTIC FRAGMENT OF HUMAN COLLAGENASE-3 (MMP-13) COMPLEXED WITH A HYDROXAMIC ACID INHIBITOR'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-FM1 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=WAY:'>WAY</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FM1 OCA].
+FM1 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=1FM1 OCA].
 ==Reference==
-High-resolution solution structure of the catalytic fragment of human collagenase-3 (MMP-13) complexed with a hydroxamic acid inhibitor., Moy FJ, Chanda PK, Chen JM, Cosmi S, Edris W, Levin JI, Powers R, J Mol Biol. 2000 Sep 22;302(3):671-89. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10986126 10986126]
+High-resolution solution structure of the catalytic fragment of human collagenase-3 (MMP-13) complexed with a hydroxamic acid inhibitor., Moy FJ, Chanda PK, Chen JM, Cosmi S, Edris W, Levin JI, Powers R, J Mol Biol. 2000 Sep 22;302(3):671-89. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10986126 10986126]
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
@@ Line 28: / Line 37: @@
 [[Category: mmp-13]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:40:03 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:10:57 2008''