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Structural Evidence That the Methionyl Aminopeptidase from Escherichia coli Is a Mononuclear Metalloprotease
  • Nathaniel J. Cosper, University of Georgia
  • Ventris M. D'Souza, Utah State University
  • Robert A. Scott, University of Georgia
  • Richard C. Holz, Marquette University
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The Co and Fe K-edge extended X-ray absorption fine structure (EXAFS) spectra of the methionyl aminopeptidase from Escherichia coli (EcMetAP) have been recorded in the presence of 1 and 2 equiv of either Co(II) or Fe(II) (i.e., [Co(II)_(EcMetAP)], [Co(II)Co(II)(EcMetAP)], [Fe(II)_(EcMetAP)], and [Fe(II)Fe(II)(EcMetAP)]). The Fourier transformed data of both [Co(II)_(EcMetAP)] and [Co(II)Co(II)(EcMetAP)] are dominated by a peak at ca. 2.05 Å, which can be fit assuming 5 light atom (N,O) scatterers at 2.04 Å. Attempts to include a Co−Co interaction (in the 2.4−4.0 Å range) in the curve-fitting parameters were unsuccessful. Inclusion of multiple-scattering contributions from the outer-shell atoms of a histidine−imidazole ring resulted in reasonable Debye−Waller factors for these contributions and a slight reduction in the goodness-of-fit value (f ‘). These data suggest that a dinuclear Co(II) center does not exist in EcMetAP and that the first Co atom is located in the histidine-ligated side of the active site. The EXAFS data obtained for [Fe(II)_(EcMetAP)] and [Fe(II)Fe(II)(EcMetAP)] indicate that Fe(II) binds to EcMetAP in a similar site to Co(II). Since no X-ray crystallographic data are available for any Fe(II)-substituted EcMetAP enzyme, these data provide the first glimpse at the Fe(II) active site of MetAP enzymes. In addition, the EXAFS data for [Co(II)Co(II)(EcMetAP)] incubated with the antiangiogenesis drug fumagillin are also presented.

Biochemistry, Vol. 40, No. 44 (October 13, 2001): 13302-13309. DOI.

Richard Holz was affiliated with the Utah State University at the time of publication.

Citation Information
Nathaniel J. Cosper, Ventris M. D'Souza, Robert A. Scott and Richard C. Holz. "Structural Evidence That the Methionyl Aminopeptidase from Escherichia coli Is a Mononuclear Metalloprotease" Biochemistry (2001) ISSN: 0006-2960
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