2o7u
From Proteopedia
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Crystal structure of K206E/K296E mutant of the N-terminal half molecule of human transferrin
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Overview
Iron uptake by humans depends on the ability of the serum protein, transferrin (Tf) to bind iron as Fe(3+) with high affinity but reversibly., Iron release into cells occurs through receptor-mediated endocytosis, aided by the lower endosomal pH of about 5.5. The protonation of a, hydrogen-bonded pair of lysines, Lys206 and Lys296, adjacent to the N-lobe, iron site of Tf has been proposed to create a repulsive interaction that, stimulates domain opening and iron release. The crystal structures of two, mutants, K206E (in which Lys206 is mutated to Glu) and K206E/K296E (in, which both lysines are mutated to Glu), have been determined. The K206E, structure (2.6 A resolution; R = 0.213, R(free) = 0.269) shows that a salt, bridge is formed between Glu206 and Lys296, thus explaining the, drastically slower iron release by this mutant. The K206E/K296E, double-mutant structure (2.8 A resolution; R = 0.232, R(free) = 0.259), shows that the Glu296 side chain moves away from Glu206, easing any, repulsive interaction and instead interacting with the iron ligand His249., The evident conformational flexibility is consistent with an alternative, model for the operation of the dilysine pair in iron release in which it, facilitates concerted proton transfer to the tyrosine ligand Tyr188 as one, step in the weakening of iron binding.
Disease
Known diseases associated with this structure: Atransferrinemia OMIM:[190000], Iron deficiency anemia, susceptibility to OMIM:[190000]
About this Structure
2O7U is a Single protein structure of sequence from Homo sapiens with FE and CO3 as ligands. Full crystallographic information is available from OCA.
Reference
Structures of two mutants that probe the role in iron release of the dilysine pair in the N-lobe of human transferrin., Baker HM, Nurizzo D, Mason AB, Baker EN, Acta Crystallogr D Biol Crystallogr. 2007 Mar;63(Pt 3):408-14. Epub 2007, Feb 21. PMID:17327678
Page seeded by OCA on Mon Nov 12 23:07:25 2007
