Coboglobins-Cobalt-Substituted Hemoglobins and Myoglobin

$546,959R01FY2015GMNIH

Northwestern University, Evanston IL

Investigators

Linked publications & trials

Paper 39665753 Paper 39392720 Paper 39293031 Paper 38690768 Paper 38645113 Paper 38587906 Paper 38308759 Paper 38187819 Paper 37956301 Paper 37417771 Paper 37307050 Paper 37115010 Paper 37026114 Paper 37018846 Paper 36914792 Paper 36282180 Paper 36251330 Paper 36108299 Paper 35657101 Paper 35320042 Paper 35319808 Paper 35258967 Paper 35012337 Paper 34981938 Paper 34498465 Paper 34161271 Paper 34155376 Paper 34074779 Paper 33996018 Paper 33935588 Paper 33574183 Paper 33464878 Paper 33372786 Paper 33326225 Paper 32966073 Paper 32176472 Paper 32022556 Paper 31527081 Paper 31509404 Paper 31441651 Paper 31310109 Paper 31274303 Paper 31073062 Paper 30807125 Paper 30403226 Paper 30355772 Paper 30346729 Paper 30323281 Paper 30205289 Paper 30183278 Paper 30095253 Paper 29954180 Paper 29739854 Paper 29675204 Paper 29590073 Paper 29575898 Paper 29440418 Paper 29283553 Paper 29042516 Paper 28989623 Paper 28851217 Paper 28850133 Paper 28768413 Paper 28571321 Paper 28383907 Paper 28177622 Paper 28121140 Paper 28001366 Paper 27878395 Paper 27777444 Paper 27746891 Paper 27698129 Paper 27529724 Paper 27527063 Paper 27500789 Paper 27465315 Paper 27174986 Paper 26788586 Paper 26750753 Paper 26717260 Paper 26716352 Paper 26652036 Paper 26636616 Paper 26603348 Paper 26419513 Paper 26000443 Paper 25923449 Paper 25853617 Paper 25849895 Paper 25741750 Paper 25686535 Paper 25137531 Paper 25136926 Paper 25059917 Paper 25046203

Abstract

DESCRIPTION (provided by applicant): Our program is devoted to answering key questions in biology through the development and application of multinuclear electron-nuclear double resonance (ENDOR) and electron spin-echo envelope modulation (ESEEM) spectroscopies to characterize transition-metal centers vital to human health and disease. Application of these techniques to intermediate states that are trapped by freeze-quench and cryoreduction methods, and are isotopically labeled by outstanding teams of collaborating chemists and biologists, can completely characterize the active-site environment of a metal ion at every stage of an enzyme's catalytic cycle. As augmented by novel kinetic protocols we have developed, these studies reveal in precise details the function of critical metal centers, not only in isolate enzymes but in living cells as well. Dramatic progress during our current grant period has inspired multiple specific aims: (i) Small-molecule activation by metalloenzymes, including Dioxygen-activation by Heme Monooxygenases and Dinitrogen Reduction by Nitrogenase; (ii) Biomimetic Mo and Fe Complexes as Models for Nitrogenase Intermediates and Paradigms for the Jahn-Taller Effect in trigonal symmetry; (iii) Radical Reactions in Metalloenzymes -The Radical SAM Superfamily; (iv) in vivo Speciation of Mn(II) - Protection from Oxidative Stress, Mechanisms of Toxicity, Probe of Physiology; (v) ATPase Co(II)/Mn(II) Transporters; (vi) ENDOR Methodology Development - Hyperfine Signs, Electron-Nuclear-Electron Triple Resonance, Q-band Resonator Development; (vii) Extending the Biological Applications of ENDOR Techniques. Many of these aims reflect longstanding efforts, while projects associated with transition-metal homeostasis that emerged this period (Mn(II) speciation, and Mn(II)/Co(II) transport) reflect a commitment to opening new areas, as explicitly expressed in the final Aim.

View original record on NIH RePORTER →