1VFD

HUMAN LACTOFERRIN, N-TERMINAL LOBE MUTANT WITH ARG 121 REPLACED BY GLU (R121E)

Summary for 1VFD

• Entry DOI: 10.2210/pdb1vfd/pdb
• Descriptor: LACTOFERRIN, FE (III) ION, CARBONATE ION, ... (4 entities in total)
• Functional Keywords: transferrin, iron transport, glycoprotein, metal-binding
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P02788
• Total number of polymer chains: 1
• Total formula weight: 36709.28

Authors

Faber, H.R.,Day, C.L.,Baker, E.N. (deposition date: 1996-10-01, release date: 1997-04-21, Last modification date: 2024-10-16)

Primary citation

Faber, H.R.,Baker, C.J.,Day, C.L.,Tweedie, J.W.,Baker, E.N.
Mutation of arginine 121 in lactoferrin destabilizes iron binding by disruption of anion binding: crystal structures of R121S and R121E mutants.
Biochemistry, 35:14473-14479, 1996

PubMed Abstract: A conserved arginine residue helps to form the synergistic anion binding site in transferrins. To probe the importance of this residue for anion binding and iron binding, Arg 121 has been mutated to Ser and Glu in N-terminal half-molecule of human lactoferrin. The two mutants, R121S and R121E, have been expressed, purified, and crystallized. Their three-dimensional structures have been determined by X-ray diffraction at 2.3 and 2.5 A resolution, respectively. The structures were determined by molecular replacement and were refined by restrained least squares methods to final R values of 0.185 and 0.204. Both mutants still bind iron but with decreased stability. The crystal structures show that destabilization of iron binding probably results from disruption of the anion binding site; mutation of Arg 121 removes one wall of the anion binding pocket and causes the synergistic carbonate ion to be displaced 0.5 A from its position in the wild-type protein. In the process it becomes partially detached from the helix N-terminus that forms the rest of the anion binding site.

PubMed: 8931543
DOI: 10.1021/bi961729g

Experimental method

X-RAY DIFFRACTION (2.5 Å)