       Document 0283
 DOCN  M9640283
 TI    Mechanistic implications from the structure of a catalytic fragment of
       Moloney murine leukemia virus reverse transcriptase.
 DT    9604
 AU    Georgiadis MM; Jessen SM; Ogata CM; Telesnitsky A; Goff SP; Hendrickson
       WA; Waksman Institute, Rutgers University, Piscataway, NJ 08855, USA.
 SO    Structure. 1995 Sep 15;3(9):879-92. Unique Identifier : AIDSLINE
       MED/96097395
 AB    BACKGROUND: Reverse transcriptase (RT) converts the single-stranded RNA
       genome of a retrovirus into a double-stranded DNA copy for integration
       into the host genome. This process requires ribonuclease H as well as
       RNA- and DNA-directed DNA polymerase activities. Although the overall
       organization of HIV-1 RT is known from previously reported crystal
       structures, no structure of a complex including a metal ion, which is
       essential for its catalytic activity, has been reported. RESULTS: Here
       we describe the structures at 1.8 Angstrum resolution of a catalytically
       active fragment of RT from Moloney murine leukemia virus (MMLV) and at
       2.6 Angstrum of a complex of this fragment with Mn2+ coordinated in the
       polymerase active site. On the basis of similarities with HIV-1 RT and
       rat DNA polymerase beta, we have modeled template/primer and
       deoxyribonucleoside 5'-triphosphate substrates into the MMLV RT
       structure. CONCLUSIONS: Our model, in the context of the disposition of
       evolutionarily conserved residues seen here at high resolution, provides
       new insights into the mechanisms of catalysis, fidelity, processivity
       and discrimination between deoxyribose and ribose nucleotides.
 DE    Amino Acid Sequence  Animal  Binding Sites  Comparative Study
       Crystallography, X-Ray  Deoxyribonucleotides/CHEMISTRY/METABOLISM  DNA
       Primers/CHEMISTRY/METABOLISM  HIV-1/ENZYMOLOGY  Metals/METABOLISM  Mice
       Models, Molecular  Molecular Sequence Data  Moloney Leukemia
       Virus/*ENZYMOLOGY  Protein Conformation  Ribonucleoproteins/CHEMISTRY
       RNA-Directed DNA Polymerase/*CHEMISTRY/*METABOLISM  Sequence Alignment
       Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

