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Publication Abstract from PubMed

The Root effect is a widespread property among fish hemoglobins whose structural basis remains largely obscure. Here we report a crystallographic and spectroscopic characterization of the non-Root-effect hemoglobin isolated from the Antarctic fish Trematomus newnesi in its deoxygenated form. The crystal structure unveils that the T state of this hemoglobin is stabilized by a strong H-bond between the side chains of Asp95alpha and Asp101beta at the alpha2beta1 and alpha1beta2 interfaces. This unexpected finding undermines the accepted paradigm that correlates the presence of this unusual H-bond with the occurrence of the Root effect. Surprisingly, the T state is characterized by an atypical flexibility of two alpha chains within the tetramer. Indeed, regions such as the CDalpha corner and the EFalpha pocket, which are normally well ordered in the T state of tetrameric hemoglobins, display high B-factors and non-continuous electron densities. This flexibility also leads to unusual distances between the heme iron and the proximal and distal His residues. These observations are in line with Raman micro-spectroscopy studies carried out both in solution and in the crystal state. The findings here presented suggest that in fish hemoglobins the Root effect may be switched off through a significant destabilization of the T state regardless of the presence of the inter-aspartic H-bond. Similar mechanisms may also operate for other non-Root effect hemoglobins. The implications of the flexibility of the CDalpha corner for the mechanism of the T-R transition in tetrameric hemoglobins are also discussed.

An order-disorder transition plays a role in switching off the Root effect in fish hemoglobins.,Vergara A, Vitagliano L, Merlino A, Sica F, Marino K, Verde C, di Prisco G, Mazzarella L J Biol Chem. 2010 Jul 7. PMID:20610398^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.