INSTITUTO DE QUIMICA, FISICA DE LOS MATERIALES, MEDIOAMBIENTE Y ENERGIA
Unidad Ejecutora - UE
Unraveling the molecular basis for ligand binding in truncated hemoglobin: the trHbO B. subtils case
LEONARDO BOECHI; PAU ARROYO MAÑEZ; F. JAVIER LUQUE; MARCELO A MARTI; DARIO A ESTRIN
PROTEINS: STRUCTURE, FUNCTION AND GENETICS
WILEY-LISS, DIV JOHN WILEY & SONS INC
Año: 2010 p. 962 - 962
Truncated hemoglobins (trHbs) are heme proteinspresent in bacteria, unicellular eukaryotes, andhigher plants. Their tertiary structure consists in a2-over-2 helical sandwich, which display typicallyan inner tunnel/cavity system for ligand migrationand/or storage. The microorganism Bacillus subtiliscontains a peculiar trHb, which does not show anevident tunnel/cavity system connecting the pro-tein active site with the solvent, and exhibits any-way a very high oxygen association rate. Moreover,resonant Raman results of CO bound protein,showed that a complex hydrogen bond networkexists in the distal cavity, making it difficult toassign unambiguously the residues involved in thestabilization of the bound ligand. To understandthese experimental results with atomistic detail, weperformed classical molecular dynamics simula-tions of the oxy, carboxy, and deoxy proteins. Thefree energy profiles for ligand migration suggestthat there is a key residue, GlnE11, that presentsan alternate conformation, in which a wide ligandmigration tunnel is formed, consistently with thekinetic data. This tunnel is topologically related tothe one found in group I trHbs. On the otherhand, the results for the CO and O2 bound proteinshow that GlnE11 is directly involved in the stabi-lization of the cordinated ligand, playing a similarrole as TyrB10 and TrpG8 in other trHbs. Ourresults not only reconcile the structural data withthe kinetic information, but also provide addi-tional insight into the general behaviour of trHbs.