9thr
Crystal structure of the human serum transferrin with Fe(III) bound at the C-lobe only (treated with DMSO)
Structural highlights
DiseaseTRFE_HUMAN Defects in TF are the cause of atransferrinemia (ATRAF) [MIM:209300. Atransferrinemia is rare autosomal recessive disorder characterized by iron overload and hypochromic anemia.[1] [2] FunctionTRFE_HUMAN Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites of absorption and heme degradation to those of storage and utilization. Serum transferrin may also have a further role in stimulating cell proliferation. Publication Abstract from PubMedThe interaction of vanadium compounds of pharmaceutical interest with metal-transport proteins like human serum transferrin (hTF) is poorly understood. Direct structural evidence identifying vanadium binding sites on hTF is still lacking. Here, the X-ray structure of the adduct formed when the potential drug [V(IV)O(acac)(2)], with acac = acetylacetonato, reacts with human serum transferrin with Fe(3+) bound at the C-lobe only (Fe(C)-hTF) has been solved and compared with new structures of Fe(C)-hTF used as controls. Structural analysis revealed the presence of a [V(V)(2)O(6)](2-) anion that can be described as a divanadate(V) anion, [V(V)(2)O(7)](4-), that has one oxygen replaced by the phenolate oxygen of Tyr188. The two vanadium centers adopt tetrahedral geometry, consistent with V(V) behavior. The binding does not alter the overall conformation of Fe(C)-hTF that retains the open conformation of the N-lobe and the closed conformation of the C-lobe, remaining able to be recognized by the transferrin receptor. First crystal structure of an adduct formed upon reaction of a vanadium compound with human serum transferrin.,Banneville AS, Lucignano R, Paolillo M, Cuomo V, Chino M, Ferraro G, Picone D, Garribba E, Cornaciu-Hoffmann I, Pica A, Merlino A Commun Chem. 2026 Jan 16. doi: 10.1038/s42004-026-01891-1. PMID:41545537[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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