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
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journal impact factor 2.079
5 year journal impact factor 1.989
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