The three-dimensional structure of NAD(P)H:quinone reductase, a flavoprotein involved in cancer chemoprotection and chemotherapy: mechanism of the two-electron reduction.

Quinone reductase [NAD(P)H:(quinone acceptor) oxidoreductase, EC 1.6.99.2], also called DT diaphorase, is a homodimeric FAD-containing enzyme that catalyzes obligatory NAD(P)H-dependent two-electron reductions of quinones and protects cells against the toxic and neoplastic effects of free radicals and reactive oxygen species arising from one-electron reductions. These two-electron reductions participate in the reductive bioactivation of cancer chemotherapeutic agents such as mitomycin C in tumor cells. Thus, surprisingly, the same enzymatic reaction that protects normal cells activates cytotoxic drugs used in cancer chemotherapy. The 2.1-A crystal structure of rat liver quinone reductase reveals that the folding of a portion of each monomer is similar to that of flavodoxin, a bacterial FMN-containing protein. Two additional portions of the polypeptide chains are involved in dimerization and in formation of the two identical catalytic sites to which both monomers contribute. The crystallographic structures of two FAD-containing enzyme complexes (one containing NADP+, the other containing duroquinone) suggest that direct hydride transfers from NAD(P)H to FAD and from FADH2 to the quinone [which occupies the site vacated by NAD(P)H] provide a simple rationale for the obligatory two-electron reductions involving a ping-pong mechanism.

I. Calculation of the length of printed lines of all the volumes in the Harvard Library, ca. 1789

This series contains one small leaf with handwritten calculations related to the number of volumes in the Harvard College Library. The verso has the note: "No. of Vol: in Harvard College 11465 vol. making one line 15380 miles long. The document is in the hand of Loammi Baldwin Sr., and may have been created in 1789 while the Library was compiling a catalog of its holdings.

I. Calculation of the length of printed lines of all the volumes in the Harvard Library, ca. 1789

This series contains one small leaf with handwritten calculations related to the number of volumes in the Harvard College Library. The verso has the note: "No. of Vol: in Harvard College 11465 vol. making one line 15380 miles long. The document is in the hand of Loammi Baldwin Sr., and may have been created in 1789 while the Library was compiling a catalog of its holdings.

La Région Méditerranéenne en 2020 et son Rôle dans le Réseau Energétjgue Européen, Vol. I: Analyse de la demande d'energie dans les PSEM (Horizons 2000-2010-2020)= The Mediterranean region in 2020 and its Role in the European Energy Network, Vol. I: Analysis of the energy demand in the SEMC (Horizons 2000-2010-2020).

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