کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
443790 692768 2010 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Tetrapyrrole binding affinity of the murine and human p22HBP heme-binding proteins
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی تئوریک و عملی
پیش نمایش صفحه اول مقاله
Tetrapyrrole binding affinity of the murine and human p22HBP heme-binding proteins
چکیده انگلیسی

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.

Figure optionsDownload high-quality image (171 K)Download as PowerPoint slideResearch highlights▶ Human and murine HBP bind HEMIN, PPIX and tetrapyrrole biosynthetic intermediates. ▶ Experimental and theoretical relative binding affinities have the same order. ▶ Tetrapyrrole molecules are recognized by HBP via multiple non-bonded interactions.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Graphics and Modelling - Volume 29, Issue 3, November 2010, Pages 396–405
نویسندگان
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