Tetrapyrrole binding affinity of the murine and human p22HBP heme-binding proteins

authors	Micaelo, NM; Macedo, AL; Goodfellow, BJ; Felix, V
nationality	International
journal	JOURNAL OF MOLECULAR GRAPHICS & MODELLING
author keywords	Heme-binding protein; Tetra pyrrole; Docking; Molecular dynamics; Binding constant
keywords	MOLECULAR-DYNAMICS; WATER MODELS; FORCE-FIELD; SIMULATION; BACTERIOFERRITIN; IDENTIFICATION; RESTRAINTS; SOLVATION; SOUL/HBP; FAMILY
abstract	We present the first systematic molecular modeling study of the binding properties of murine (mHBP) and human (hHBP) p22HBP protein (heme-binding protein) with four tetrapyrrole ring systems belonging to the heme biosynthetic pathway: iron protoporphyrin IX (HEMIN), protoporphyrin IX (PPIX), coproporphyrin III (CPIII), coproporphyrin I (CPI). The relative binding affinities predicted by our computational study were found to be similar to those observed experimentally, providing a first rational structural analysis of the molecular recognition mechanism, by p22HBP, toward a number of different tetrapyrrole ligands. To probe the structure of these p22HBP protein complexes, docking, molecular dynamics and MM-PBSA methodologies supported by experimental NMR ring current shift data have been employed. The tetrapyrroles studied were found to bind murine p22HBP with the following binding affinity order: HEMIN > PPIX > CPIII > CPI, which ranged from -22.2 to -6.1 kcal/mol. In general, the protein-tetrapyrrole complexes are stabilized by non-bonded interactions between the tetrapyrrole propionate groups and basic residues of the protein, and by the preferential salvation of the complex compared to the unbound components. (C) 2010 Elsevier Inc. All rights reserved.
publisher	ELSEVIER SCIENCE INC
issn	1093-3263
year published	2010
volume	29
issue	3
beginning page	396
ending page	405
digital object identifier (doi)	10.1016/j.jmgm.2010.07.008
web of science category	Biochemical Research Methods; Biochemistry & Molecular Biology; Computer Science, Interdisciplinary Applications; Crystallography; Mathematical & Computational Biology
subject category	Biochemistry & Molecular Biology; Computer Science; Crystallography; Mathematical & Computational Biology
unique article identifier	WOS:000285402500011