1l6j: Difference between revisions

Revision as of 14:41, 21 February 2008

Crystal structure of human matrix metalloproteinase MMP9 (gelatinase B).

OverviewOverview

The X-ray crystal structure of the proform of human matrix metalloproteinase MMP9 has been solved to 2.5 A resolution. The construct includes the prodomain, the catalytic domain and three FnII (fibronectin type II) domains. The prodomain is inserted into the active-site cleft, blocking access to the catalytic zinc. Comparison with the crystal structure of the most closely related MMP, MMP2, indicates that the conformations of residues in the active-site cleft and in the cysteine-switch peptide of the prodomain are highly conserved and that design of MMP9-specific inhibitors will be challenging. In common with MMP2, the MMP9 S1' inhibitor-binding pocket is large compared with that of other MMPs. One small point of difference in the S1' binding pockets of MMP9 and MMP2 may provide an opportunity to explore the design of specific inhibitors. The side chain of Arg424 in MMP9 is angled slightly away from the S1' pocket when compared with the corresponding residue in MMP2, Thr424. The secondary structure of the FnII domains is conserved between the two closely related MMPs, although the second FnII domain makes no contact with the catalytic domain in MMP9, while the same domain in MMP2 has a substantial area of interaction with the catalytic domain.

About this StructureAbout this Structure

1L6J is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Gelatinase B, with EC number 3.4.24.35 Full crystallographic information is available from OCA.

ReferenceReference

Structure of the C-terminally truncated human ProMMP9, a gelatin-binding matrix metalloproteinase., Elkins PA, Ho YS, Smith WW, Janson CA, D'Alessio KJ, McQueney MS, Cummings MD, Romanic AM, Acta Crystallogr D Biol Crystallogr. 2002 Jul;58(Pt 7):1182-92. Epub 2002, Jun 20. PMID:12077439

Page seeded by OCA on Thu Feb 21 13:41:53 2008

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

OCA

@@ Line 4: / Line 4: @@
 ==Overview==
-The X-ray crystal structure of the proform of human matrix, metalloproteinase MMP9 has been solved to 2.5 A resolution. The construct, includes the prodomain, the catalytic domain and three FnII (fibronectin, type II) domains. The prodomain is inserted into the active-site cleft, blocking access to the catalytic zinc. Comparison with the crystal, structure of the most closely related MMP, MMP2, indicates that the, conformations of residues in the active-site cleft and in the, cysteine-switch peptide of the prodomain are highly conserved and that, design of MMP9-specific inhibitors will be challenging. In common with, MMP2, the MMP9 S1' inhibitor-binding pocket is large compared with that of, other MMPs. One small point of difference in the S1' binding pockets of, MMP9 and MMP2 may provide an opportunity to explore the design of specific, inhibitors. The side chain of Arg424 in MMP9 is angled slightly away from, the S1' pocket when compared with the corresponding residue in MMP2, Thr424. The secondary structure of the FnII domains is conserved between, the two closely related MMPs, although the second FnII domain makes no, contact with the catalytic domain in MMP9, while the same domain in MMP2, has a substantial area of interaction with the catalytic domain.
+The X-ray crystal structure of the proform of human matrix metalloproteinase MMP9 has been solved to 2.5 A resolution. The construct includes the prodomain, the catalytic domain and three FnII (fibronectin type II) domains. The prodomain is inserted into the active-site cleft, blocking access to the catalytic zinc. Comparison with the crystal structure of the most closely related MMP, MMP2, indicates that the conformations of residues in the active-site cleft and in the cysteine-switch peptide of the prodomain are highly conserved and that design of MMP9-specific inhibitors will be challenging. In common with MMP2, the MMP9 S1' inhibitor-binding pocket is large compared with that of other MMPs. One small point of difference in the S1' binding pockets of MMP9 and MMP2 may provide an opportunity to explore the design of specific inhibitors. The side chain of Arg424 in MMP9 is angled slightly away from the S1' pocket when compared with the corresponding residue in MMP2, Thr424. The secondary structure of the FnII domains is conserved between the two closely related MMPs, although the second FnII domain makes no contact with the catalytic domain in MMP9, while the same domain in MMP2 has a substantial area of interaction with the catalytic domain.
 ==About this Structure==
@@ Line 14: / Line 14: @@
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
-[[Category: Alessio, K.J.D.]]
+[[Category: Alessio, K J.D.]]
-[[Category: Cummings, M.D.]]
+[[Category: Cummings, M D.]]
-[[Category: Elkins, P.A.]]
+[[Category: Elkins, P A.]]
-[[Category: Ho, Y.S.]]
+[[Category: Ho, Y S.]]
-[[Category: Janson, C.A.]]
+[[Category: Janson, C A.]]
-[[Category: McQueney, M.S.]]
+[[Category: McQueney, M S.]]
-[[Category: Romanic, A.M.]]
+[[Category: Romanic, A M.]]
-[[Category: Smith, W.W.]]
+[[Category: Smith, W W.]]
 [[Category: CA]]
 [[Category: ZN]]
 [[Category: twisted beta sheet flanked by helices]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:16:42 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:41:53 2008''