1oo9: Difference between revisions
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|SITE= | |SITE= | ||
|LIGAND= | |LIGAND= | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/Stromelysin_1 Stromelysin 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.17 3.4.24.17] | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Stromelysin_1 Stromelysin 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.17 3.4.24.17] </span> | ||
|GENE= MMP3 OR STMY1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), TIMP1 OR TIMP OR CLGI ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= MMP3 OR STMY1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), TIMP1 OR TIMP OR CLGI ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1uea|1UEA]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1oo9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oo9 OCA], [http://www.ebi.ac.uk/pdbsum/1oo9 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1oo9 RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
Crystal structures of catalytic domains of MMP-3 and MT1-MMP bound to TIMP-1 or TIMP-2, respectively, differ in the orientation of the TIMP in the MMP active site. The orientation in solution of N-TIMP-1 in the MMP-3 active site has been investigated using residual dipolar couplings (RDCs). Fitting of the RDCs to the X-ray structures of the complexes suggests general agreement with the orientation of crystalline MMP-3(DeltaC) and TIMP-1 and a large disparity from the orientation of crystalline MT1-MMP(DeltaC) and TIMP-2. Rigid body docking of MMP-3 and N-TIMP-1 X-ray coordinates using RDCs and intermolecular NOEs provided a time-averaged orientation in solution differing from the crystal structure by a 5 degrees rotation toward the MT1-MMP(DeltaC)/TIMP-2 orientation. The slight discrepancy in orientations in solution and crystal lies within the experimental uncertainties. Intermolecular NOEs used in the docking corroborated the accuracy of mapping the interface by a paramagnetic NMR footprinting assay, a potential alternative source of contacts for docking. Some uncertainty in the N-TIMP-1 orientation in the MMP-3 active site, coupled with microsecond to millisecond fluctuations of the MMP-binding ridge of N-TIMP-1 in the complex and flexibility in MMP-3(DeltaC) S(1)' to S(3)' subsites, leaves open the possibility that N-TIMP-1 might dynamically pivot a few degrees or more in the arc toward the MT1-MMP(DeltaC)/TIMP-2 orientation. Differing TIMP orientations in MMP active sites are more likely to result from structural differences in TIMP AB hairpin loops than from crystal packing artifacts. | Crystal structures of catalytic domains of MMP-3 and MT1-MMP bound to TIMP-1 or TIMP-2, respectively, differ in the orientation of the TIMP in the MMP active site. The orientation in solution of N-TIMP-1 in the MMP-3 active site has been investigated using residual dipolar couplings (RDCs). Fitting of the RDCs to the X-ray structures of the complexes suggests general agreement with the orientation of crystalline MMP-3(DeltaC) and TIMP-1 and a large disparity from the orientation of crystalline MT1-MMP(DeltaC) and TIMP-2. Rigid body docking of MMP-3 and N-TIMP-1 X-ray coordinates using RDCs and intermolecular NOEs provided a time-averaged orientation in solution differing from the crystal structure by a 5 degrees rotation toward the MT1-MMP(DeltaC)/TIMP-2 orientation. The slight discrepancy in orientations in solution and crystal lies within the experimental uncertainties. Intermolecular NOEs used in the docking corroborated the accuracy of mapping the interface by a paramagnetic NMR footprinting assay, a potential alternative source of contacts for docking. Some uncertainty in the N-TIMP-1 orientation in the MMP-3 active site, coupled with microsecond to millisecond fluctuations of the MMP-binding ridge of N-TIMP-1 in the complex and flexibility in MMP-3(DeltaC) S(1)' to S(3)' subsites, leaves open the possibility that N-TIMP-1 might dynamically pivot a few degrees or more in the arc toward the MT1-MMP(DeltaC)/TIMP-2 orientation. Differing TIMP orientations in MMP active sites are more likely to result from structural differences in TIMP AB hairpin loops than from crystal packing artifacts. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: protein-protein complex]] | [[Category: protein-protein complex]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:48:07 2008'' | ||