4JIJ
Crystal structure of an inactive mutant of MMP-9 catalytic domain in complex with a fluorogenic synthetic peptidic substrate
Summary for 4JIJ
| Entry DOI | 10.2210/pdb4jij/pdb |
| Related | 2OW0 2OW1 4H1Q 4H2E 4H3X 4H82 4HMA 4JQG 4JXA |
| Descriptor | fluorogenic peptidic substrate (8MC)PLG(PHI)(DNW)AR(NH2), GLYCEROL, Matrix metalloproteinase-9, ... (11 entities in total) |
| Functional Keywords | hydrolase substrate complex, zincin-like, gelatinase, collagenase, catalytic domain, hydrolase-substrate complex, hydrolase/substrate |
| Biological source | Homo sapiens (human) More |
| Cellular location | Secreted, extracellular space, extracellular matrix : P14780 |
| Total number of polymer chains | 4 |
| Total formula weight | 40533.77 |
| Authors | Stura, E.A.,Vera, L.,Cassar-Lajeunesse, E.,Tranchant, I.,Amoura, M.,Dive, V. (deposition date: 2013-03-06, release date: 2014-03-12, Last modification date: 2023-12-06) |
| Primary citation | Tranchant, I.,Vera, L.,Czarny, B.,Amoura, M.,Cassar, E.,Beau, F.,Stura, E.A.,Dive, V. Halogen Bonding Controls Selectivity of FRET Substrate Probes for MMP-9. Chem.Biol., 21:408-413, 2014 Cited by PubMed Abstract: Matrix metalloproteinases (MMPs) are a large family of zinc-dependent endoproteases that catalyze cleavage of extracellular matrix and nonmatrix proteins. MMPs play a role in tissue remodeling, and their uncontrolled activity is associated with number of diseases, including tumor metastasis. Thus, there is a need to develop methods to monitor MMP activity, and number of probes has been previously described. The key problem many probes encounter is the issue of selectivity, since 23 human MMPs, despite playing different physiological roles, have structurally similar active sites. Here, we introduce the halogen bonding concept into the probe design and show that the probe containing iodine exhibits an unprecedented selectivity for MMP-9. We provide structure-based explanation for the selectivity, confirming that it is due to formation of the halogen bond that supports catalysis, and we highlight the value of exploring halogen bonding in the context of selective probe design. PubMed: 24583051DOI: 10.1016/j.chembiol.2014.01.008 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.698 Å) |
Structure validation
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