1z3j
From Proteopedia
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'''Solution Structure of MMP12 in the presence of N-isobutyl-N-4-methoxyphenylsulfonyl]glycyl hydroxamic acid (NNGH)''' | '''Solution Structure of MMP12 in the presence of N-isobutyl-N-4-methoxyphenylsulfonyl]glycyl hydroxamic acid (NNGH)''' | ||
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[[Category: Terni, B.]] | [[Category: Terni, B.]] | ||
[[Category: Turano, P.]] | [[Category: Turano, P.]] | ||
| - | [[Category: | + | [[Category: Macrophage metalloelastase]] |
| - | [[Category: | + | [[Category: Mmp-12]] |
| - | [[Category: | + | [[Category: Nngh]] |
| - | [[Category: | + | [[Category: Solution structure]] |
| - | [[Category: | + | [[Category: Zinc]] |
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Revision as of 14:08, 3 May 2008
Solution Structure of MMP12 in the presence of N-isobutyl-N-4-methoxyphenylsulfonyl]glycyl hydroxamic acid (NNGH)
Overview
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.
About this Structure
1Z3J is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Conformational variability of matrix metalloproteinases: beyond a single 3D structure., Bertini I, Calderone V, Cosenza M, Fragai M, Lee YM, Luchinat C, Mangani S, Terni B, Turano P, Proc Natl Acad Sci U S A. 2005 Apr 12;102(15):5334-9. Epub 2005 Apr 4. PMID:15809432 Page seeded by OCA on Sat May 3 17:08:25 2008
