Alistair J Fielding

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Heme enzymes activate oxygen through formation of transient iron-oxo (ferryl) intermediates of the heme iron. A long-standing question has been the nature of the iron-oxygen bond and, in particular, the protonation state. We present neutron structures of the ferric derivative of cytochrome c peroxidase and its ferryl intermediate; these allow direct(More)
Spin labelling is a chemical technique that enables the integration of a molecule containing an unpaired electron into another framework for study. Given the need to understand the structure, dynamics, and conformational changes of biomacromolecules, spin labelling provides a relatively non-intrusive technique and has certain advantages over X-ray(More)
Psi factor producing oxygenases (Ppos) are fusion proteins consisting of a peroxidase-like functionality in the N-terminus and a P450-fold in the C-terminal part of the polypeptide chain. It was shown that they are responsible for the production of oxidized fatty acids that play a pivotal role in the control of fungal colonization of plant and mammalian(More)
A quantum mechanical (QM) method rooted on density functional theory (DFT) has been employed to determine conformations of the methane-thiosulfonate spin label (MTSL) attached to a fragment extracted from the activation loop of Aurora-A kinase. The features of the calculated energy surface revealed low energy barriers between isoenergetic minima, and the(More)
The flavoenzyme monoamine oxidase (MAO) regulates mammalian behavioral patterns by modulating neurotransmitters such as adrenaline and serotonin. The mechanistic basis which underpins this enzyme is far from agreed upon. Reported herein is that the combination of a synthetic flavin and alloxan generates a catalyst system which facilitates biomimetic amine(More)
Heterodisulfide reductase (Hdr) is a key enzyme in the energy metabolism of methanogenic archaea. The enzyme catalyzes the reversible reduction of the heterodisulfide (CoM-S-S-CoB) to the thiol coenzymes M (CoM-SH) and B (CoB-SH). Cleavage of CoM-S-S-CoB at an unusual FeS cluster reveals unique substrate chemistry. The cluster is fixed by cysteines of two(More)
Catalytic heme enzymes carry out a wide range of oxidations in biology. They have in common a mechanism that requires formation of highly oxidized ferryl intermediates. It is these ferryl intermediates that provide the catalytic engine to drive the biological activity. Unravelling the nature of the ferryl species is of fundamental and widespread importance.(More)
The understanding of kinase structure is mostly based on protein crystallography, which is limited by the requirement to trap molecules within a crystal lattice. Characterisation of the conformations of the activation loop in solution, are important to enhance the understanding of molecular processes related to diseases and to support the discovery of small(More)
The structure of protein kinases has been extensively studied by protein crystallography. Conformational movement of the kinase activation loop is thought to be crucial for regulation of activity; however, in many cases the position of the activation loop in solution is unknown. Protein kinases are an important class of therapeutic target and kinase(More)
Platinum(ii) complexes of mixed-valent radicals derived from cyclotricatechylene, a macrocyclic tris-dioxolene Platinum(ii) complexes of mixed-valent radicals derived from cyclotricatechylene, a macrocyclic tris-dioxolene. Users may access full items free of charge; copies of full text items generally can be reproduced, displayed or performed and given to(More)