1lfi
METAL SUBSTITUTION IN TRANSFERRINS: THE CRYSTAL STRUCTURE OF HUMAN COPPER-LACTOFERRIN AT 2.1 ANGSTROMS RESOLUTION
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OverviewOverview
The structural consequences of binding a metal other than iron to a, transferrin have been examined by crystallographic analysis of human, copper-lactoferrin, Cu2Lf. X-ray diffraction data were collected from, crystals of Cu2Lf, using a diffractometer, to 2.6-A resolution, and, oscillation photography on a synchrotron source, to 2.1-A resolution. The, structure was refined crystallographically, by restrained least-squares, methods, starting with a model based on the isomorphous diferric structure, from which the ligands, metal ions, anions, and solvent molecules had been, deleted. The final model, comprising 5321 protein atoms (691 residues), 2, Cu2+ ions, 2 (bi)carbonate ions, and 308 solvent molecules has good, stereochemistry (rms deviation of bond lengths from standard values of, 0.018 A) and gives a crystallographic R value of 0.196 for 43,525, reflections in the range 7.5-2.1-A resolution. The copper coordination is, different in the two binding sites. In the N-terminal site, the geometry, is square pyramidal, with equatorial bonds to Asp 60, Tyr 192, His 253, and a monodentate anion and a longer apical bond to Tyr 92. In the, C-terminal site, the geometry is distorted octahedral, with bonds to Asp, 395, Tyr 435, Tyr 528, and His 597 and an asymmetrically bidentate anion., The protein structure is the same as for the diferric protein, Fe2Lf, demonstrating that the closure of the protein domains over the metal is, the same in each case irrespective of whether Fe3+ or Cu2+ is bound and, that copper could be transported and delivered to cells equally well as, iron. The differences in metal coordination are achieved by small, movements of the metal ion and anion within each binding site, which do, not affect the protein structure.
DiseaseDisease
Known disease associated with this structure: Deafness, autosomal dominant 1 OMIM:[602121]
About this StructureAbout this Structure
1LFI is a Single protein structure of sequence from [1] with NAG, CU and CO3 as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Metal substitution in transferrins: the crystal structure of human copper-lactoferrin at 2.1-A resolution., Smith CA, Anderson BF, Baker HM, Baker EN, Biochemistry. 1992 May 12;31(18):4527-33. PMID:1581307
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