2011
DOI: 10.1074/jbc.m111.285213
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The Interface between Catalytic and Hemopexin Domains in Matrix Metalloproteinase-1 Conceals a Collagen Binding Exosite

Abstract: Background: The precise role of the hemopexin domain of matrix metalloproteinase-1 (MMP-1) in collagenolysis is unknown. Results: The hemopexin domain collagen binding site is on ␤-propeller blades 1 and 2, and includes a Phe that is buried in the interface with the catalytic domain in the MMP-1 crystal structure. Conclusion: Domain dislocation is required for exosite exposure. Significance: MMP-1 may undergo significant domain rearrangements during collagenolysis.

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Cited by 54 publications
(82 citation statements)
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“…Similar R g values were also obtained for the highest MO structures without inclusion of the SAXS restraints in the calculations. This range of R g is in better agreement with the experimentally determined values from the SAXS data alone (28.5-29.0 Å) (8,15), indicating that x-ray structures were more compact than the average solution conformation. Furthermore, the relative orientations of HPX and CAT domains in the structures with the highest MO were different from those in the x-ray crystallographic structures.…”
Section: Volume 288 • Number 42 • October 18 2013supporting
confidence: 78%
See 2 more Smart Citations
“…Similar R g values were also obtained for the highest MO structures without inclusion of the SAXS restraints in the calculations. This range of R g is in better agreement with the experimentally determined values from the SAXS data alone (28.5-29.0 Å) (8,15), indicating that x-ray structures were more compact than the average solution conformation. Furthermore, the relative orientations of HPX and CAT domains in the structures with the highest MO were different from those in the x-ray crystallographic structures.…”
Section: Volume 288 • Number 42 • October 18 2013supporting
confidence: 78%
“…Different generalized order parameters as well as different scaling factors of the components of the anisotropy tensor indicated that the HPX domain motion caused different motional averaging for the different metals, because of the different rhombicity and directions of the principal axes of the anisotropy tensors. SAXS data, previously measured for MMP-1 in solution under the same experimental conditions as utilized here (8,15), also indicated that the structure of the protein cannot be described by the crystallographic conformation alone, but that ensembles with closed and more extended conformations must be considered, further indicating that the protein experiences noticeable flexibility.…”
Section: Resultsmentioning
confidence: 99%
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“…Comparison of the crystal structure of proMMP-1 (29) with the structure of the activated form of MMP-1(E200A) (6,7) suggested that the Cat-Hpx linker region confers interdomain flexibility. Such flexing was further demonstrated for MMP-1 by NMR and small angle X-ray scattering studies (40,41) and seems to be a common property of MMPs (42,43). Our crystal structure of MMP-1 bound to collagen has a more closed conformation than free MMP-1 (SI Appendix, Fig.…”
Section: Discussionmentioning
confidence: 85%
“…The mechanistic relationship between cleavage of a linear sequence, as studied here, and cleavage of 3D triple helical collagen by some MMPs is not entirely clear. In almost all cases, the hemopexin domain, which is adjacent to the catalytic domain, is required for cleaving collagen (40)(41)(42), probably by providing an ancillary binding surface. Furthermore, recent work indicates that the MMP-1 collagenase is engaged in an intermittent diffusion alongside the collagen fibril, with the bias component being attributed to proteolysis of substrate (43).…”
Section: Discussionmentioning
confidence: 99%