View source for 1oo9

[[Image:1oo9.jpg|left|200px]]<br /><applet load="1oo9" size="350" color="white" frame="true" align="right" spinBox="true" 
caption="1oo9" />
'''Orientation in Solution of MMP-3 Catalytic Domain and N-TIMP-1 from Residual Dipolar Couplings'''<br />

==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.

==Disease==
Known diseases associated with this structure: Coronary heart disease, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=185250 185250]], Sorsby fundus dystrophy OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188826 188826]]

==About this Structure==
1OO9 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OO9 OCA]. 

==Reference==
Global orientation of bound MMP-3 and N-TIMP-1 in solution via residual dipolar couplings., Arumugam S, Van Doren SR, Biochemistry. 2003 Jul 8;42(26):7950-8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12834347 12834347]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Stromelysin 1]]
[[Category: Arumugam, S.]]
[[Category: Doren, S R.Van.]]
[[Category: protein-protein complex]]

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