A structural basis for the activity of retro-Diels–Alder catalytic antibodies: Evidence for a catalytic aromatic residue
| العنوان: | A structural basis for the activity of retro-Diels–Alder catalytic antibodies: Evidence for a catalytic aromatic residue |
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| المؤلفون: | Martine T. Reymond, Beda M. Stadler, Jean-Louis Reymond, Monique Vogel, Nicolas Bensel, Ulrich Baumann, Marina Hugot |
| المصدر: | Proceedings of the National Academy of Sciences. 99:9674-9678 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2002. |
| سنة النشر: | 2002 |
| مصطلحات موضوعية: | Models, Molecular, Protein Conformation, Stereochemistry, Molecular Sequence Data, Antibodies, Catalytic, Crystallography, X-Ray, Catalysis, Immunoglobulin Fab Fragments, chemistry.chemical_compound, Residue (chemistry), Protein structure, Transition state analog, Catalytic Domain, Amino Acid Sequence, Cloning, Molecular, DNA Primers, Multidisciplinary, Base Sequence, Sequence Homology, Amino Acid, Bicyclic molecule, Chemistry, Aromaticity, Nitroxyl, Biological Sciences, Apoproteins, Haptens, Sequence Alignment |
| الوصف: | The nitroxyl synthase catalytic antibodies 10F11, 9D9, and 27C5 catalyze the release of nitroxyl from a bicyclic pro-drug by accelerating a retro-Diels–Alder reaction. The Fabs (antigen-binding fragments) of these three catalytic antibodies were cloned and sequenced. Fab 9D9 was crystallized in the apo-form and in complex with one transition state analogue of the reaction. Crystal structures of Fab 10F11 in complex with ligands mimicking substrate, transition state, and product have been determined at resolutions ranging from 1.8 to 2.3 Å. Antibodies 9D9 and 10F11 show increased shape complementarity (as quantified by the program sc ) to the hapten and to a modeled transition state as compared with substrate and product. The shape complementarity is mediated to a large extent by an aromatic residue (tyrosine or tryptophan) at the bottom of the hydrophobic active pocket, which undergoes π-stacking interactions with the aromatic rings of the ligands. Another factor contributing to the different reactivity of the regioisomers probably arises because of hydrogen-bonding interactions between the nitroxyl bridge and the backbone amide of PheH101 and possibly a conserved water molecule. |
| تدمد: | 1091-6490 0027-8424 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::25a99a2b199085c7f9725c9e2fd5ecf0Test https://doi.org/10.1073/pnas.142286599Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....25a99a2b199085c7f9725c9e2fd5ecf0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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