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

Nuno M Micaelo, Anjos L Macedo, Brian J Goodfellow, Vítor Félix

Departamento de Química, CICECO and Secção Autónoma de Ciências da Saúde, Universidade de Aveiro, 3810-193 Aveiro, Portugal.

Journal of molecular graphics & modelling 2010 Nov

filter terms:

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 solvation of the complex compared to the unbound components. Copyright © 2010 Elsevier Inc. All rights reserved.

Citation

Nuno M Micaelo, Anjos L Macedo, Brian J Goodfellow, Vítor Félix. Tetrapyrrole binding affinity of the murine and human p22HBP heme-binding proteins. Journal of molecular graphics & modelling. 2010 Nov;29(3):396-405