Summary
PDB 1Y93 deposited: 2004-12-14 modified: 2011-07-13
Title Crystal structure of the catalytic domain of human MMP12 complexed with acetohydroxamic acid at atomic resolution
Authors Bertini, I., Calderone, V., Cosenza, M., Fragai, M., Lee, Y.-M., Luchinat, C., Mangani, S., Terni, B., Turano, P.
Method X-RAY DIFFRACTION
Structure factors resolution 1.03 rfactor 0.15563 rfree 0.16787
DPI 0.08 theoretical min: 0.03
Related PDB Entries 1OS2 1OS9 1RMZ 1YCM 1Z3J 3EHX 3EHY 3F15 3F16 3F17 3F18 3F19 3F1A 4IJO
Citations

"The structures of the catalytic domain of matrix metalloproteinase 12 in the presence of acetohydroxamic acid and N-isobutyl-N-[4-methoxyphenylsulfonyl]glycyl hydroxamic acid have been solved by x-ray diffraction in the crystalline state at 1.0 and 1.3-A resolution, respectively, and compared with the previously published x-ray structure at 1.2-A resolution of the adduct with batimastat. The structure of the N-isobutyl-N-[4-methoxyphenylsulfonyl]glycyl hydroxamic acid adduct has been solved by NMR in solution. The three x-ray structures and the solution structure are similar but not identical to one another, the differences being sizably higher in the loops. We propose that many of the loops show a dynamical behavior in solution on a variety of time scales. Different conformations of some flexible regions of the protein can be observed as ""frozen"" in different crystalline environments. The mobility in solution studied by NMR reveals conformational equilibria in accessible time scales, i.e., from 10(-5) s to ms and more. Averaging of some residual dipolar couplings is consistent with further motions down to 10(-9) s. Finally, local thermal motions of each frozen conformation in the crystalline state at 100 K correlate well with local motions on the picosecond time scale. Flexibility/conformational heterogeneity in crucial parts of the catalytic domain is a rule rather than an exception in matrix metalloproteinases, and its extent may be underestimated by inspection of one x-ray structure. Backbone flexibility may play a role in the difficulties encountered in the design of selective inhibitors, whereas it may be a requisite for substrate binding and broad substrate specificity."

Proc.Natl.Acad.Sci.Usa 2005 Apr; 102(15):5334-5339 doi:10.1073/pnas.0407106102

Angew.Chem.Int.Ed.Engl. 2003 Jun; 42(23):2673-2676 doi:10.1002/anie.200350957

Cross References
Database source Identifier Description
PubMed 15809432 PNASA6
PubMed 12813751
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
1Y93/0 1Y93 0 monomer 0 1 6 1406