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

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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.
Original languageUnknown
Pages (from-to)396-405
JournalJournal Of Molecular Graphics & Modelling
Volume29
Issue number3
DOIs
Publication statusPublished - 1 Jan 2010

Keywords

    Cite this

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    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 salvation of the complex compared to the unbound components. (C) 2010 Elsevier Inc. All rights reserved.",
    keywords = "Binding, models, constant, solvation, simulation, force-field, Molecular, water, pyrrole, soul/hbp, dynamics, molecular-dynamics, identification, protein, bacterioferritin, Docking, restraints, Heme-binding, family, Tetra",
    author = "Macedo, {Maria dos Anjos L{\'o}pez de}",
    year = "2010",
    month = "1",
    day = "1",
    doi = "10.1016/j.jmgm.2010.07.008",
    language = "Unknown",
    volume = "29",
    pages = "396--405",
    journal = "Journal Of Molecular Graphics & Modelling",
    issn = "1093-3263",
    publisher = "Elsevier Science B.V., Amsterdam.",
    number = "3",

    }

    TY - JOUR

    T1 - Tetrapyrrole binding affinity of the murine and human p22HBP heme-binding proteins

    AU - Macedo, Maria dos Anjos López de

    PY - 2010/1/1

    Y1 - 2010/1/1

    N2 - 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.

    AB - 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.

    KW - Binding

    KW - models

    KW - constant

    KW - solvation

    KW - simulation

    KW - force-field

    KW - Molecular

    KW - water

    KW - pyrrole

    KW - soul/hbp

    KW - dynamics

    KW - molecular-dynamics

    KW - identification

    KW - protein

    KW - bacterioferritin

    KW - Docking

    KW - restraints

    KW - Heme-binding

    KW - family

    KW - Tetra

    U2 - 10.1016/j.jmgm.2010.07.008

    DO - 10.1016/j.jmgm.2010.07.008

    M3 - Article

    VL - 29

    SP - 396

    EP - 405

    JO - Journal Of Molecular Graphics & Modelling

    JF - Journal Of Molecular Graphics & Modelling

    SN - 1093-3263

    IS - 3

    ER -