18 research outputs found

    Radical SAM enzyme QueE defines a new minimal core fold and metal-dependent mechanism

    Get PDF
    7-carboxy-7-deazaguanine synthase (QueE) catalyzes a key S-adenosyl-L-methionine (AdoMet)- and Mg[superscript 2+]-dependent radical-mediated ring contraction step, which is common to the biosynthetic pathways of all deazapurine-containing compounds. QueE is a member of the AdoMet radical superfamily, which employs the 5′-deoxyadenosyl radical from reductive cleavage of AdoMet to initiate chemistry. To provide a mechanistic rationale for this elaborate transformation, we present the crystal structure of a QueE along with structures of pre- and post-turnover states. We find that substrate binds perpendicular to the [4Fe-4S]-bound AdoMet, exposing its C6 hydrogen atom for abstraction and generating the binding site for Mg[superscript 2+], which coordinates directly to the substrate. The Burkholderia multivorans structure reported here varies from all other previously characterized members of the AdoMet radical superfamily in that it contains a hypermodified ([β [subscript 6] over α [subscript 3]]) protein core and an expanded cluster-binding motif, CX[subscript 14]CX[subscript 2]C.United States. Dept. of Energy. Office of Biological and Environmental ResearchUnited States. Dept. of Energy. Office of Basic Energy SciencesNational Center for Research Resources (U.S.) (P41RR012408)National Institute of General Medical Sciences (U.S.) (P41GM103473)National Center for Research Resources (U.S.) (5P41RR015301-10)National Institute of General Medical Sciences (U.S.) (8 P41 GM 103403-10)United States. Dept. of Energy (Contract DE-AC02-06CH11357

    Towards ultra-low power bio-inspired processing

    No full text
    The natural world is analogue and yet the modern microelectronic world with which we interact represents real world data using discrete quantities manipulated by logic. In the human space, we are entering a new wave of body-worn biosensor technology for medical diagnostics and therapy. This new trend is beginning to see the processing interface move back to using continuous quantities, which are more or less in line with the biological processes. We label this computational paradigm “bio-inspired” because of the ability of silicon chip technology which enables the use of inherent device physics, allowing us to approach the computational efficiencies of biology. From a conceptual viewpoint, this has led to a number of more specific morphologies including neuromorphic and retinomorphic processing. These have led scientists to model biological systems such as the cochlea and retina and gain not only superior computational resource efficiency (to conventional hearing aid or camera technology), but also an increased understanding of biological and neurological processes
    corecore