RNA Polymerase: Catalytic Mechanisms and Inhibitors

Abstract

INTRODUCTION
Prokaryotic RNA polymerase is a complex oligomeric enzyme with the inherent capacity to catalyze the specific transcription of DNA (Chamberlin 1974a,b).

RNA polymerase consists of a catalytically competent core with four subunits (β′βα₂) and a fifth dissociable subunit (σ) responsible for the selection of specific sites for chain initiation (Burgess 1971). The assignment of specific functions to the various subunits is somewhat tentative, particularly due to the lack of knowledge about the primary and three-dimensional structure of the enzyme. Current evidence suggests that the β′ subunit is involved in template-binding and that the β subunit contains at least part of the catalytic center, but the function of the α subunit is unknown. From low-angle X-ray measurements (Pilz, Kratky and Rabussay 1972) it has been concluded that the enzyme is an elongated structure with a radius of gyration of about 60 Å and a maximal dimension of about 150 Å, allowing for a contact length of about three full turns of the DNA helix, or 30–40 base pairs.

The process of RNA synthesis has been subdivided functionally into a sequence of four steps (Anthony, Zeszotek and Goldthwait 1966): (1) template-binding, (2) chain initiation, (3) chain elongation and (4) chain termination. Each of these events consists of many elementary steps and has a high order of thermodynamic and kinetic complexity. Nonetheless, this formalism, which is well supported by experimental evidence, implies the existence of four distinct structural domains on the enzyme, designated here as sites for the sake of simplicity:...