title: Tetrapyrrole binding affinity of the murine and human p22HBP heme-binding proteins.
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 solvation of the complex compared to the unbound components.
authors.affiliation: Departamento de Química, CICECO and Secção Autónoma de Ciências da Saúde, Universidade de Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Nuno M
authors.initials: NM
authors.lastname: Micaelo
authors.forename: Anjos L
authors.initials: AL
authors.lastname: Macedo
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Goodfellow
authors.forename: Vítor
authors.initials: V
authors.lastname: Félix
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D003306:Coproporphyrins / Q000737:chemistry / Q000378:metabolism; D006418:Heme / Q000096:biosynthesis / Q000737:chemistry; D000081062:Heme-Binding Proteins; D006420:Hemeproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006427:Hemin / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D051379:Mice; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D011487:Protein Conformation; D011524:Protoporphyrins / Q000737:chemistry / Q000378:metabolism; D045725:Tetrapyrroles / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D003306:Coproporphyrins; C000631029:HEBP1 protein, human; C469231:Hebp1 protein, mouse; D000081062:Heme-Binding Proteins; D006420:Hemeproteins; D011524:Protoporphyrins; D045725:Tetrapyrroles; C026971:coproporphyrin III; D006418:Heme; C031467:coproporphyrin I; D006427:Hemin; C028025:protoporphyrin IX