DnaB helicase

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PDB 1jwe EBI

DnaB helicase is an enzyme that plays a crucial role in the DNA replication process in bacteria. It is a motor protein that travels along the DNA strand, unwinding the double helix into two single strands, allowing each strand to be copied. This unwinding is essential for the replication machinery to access the DNA template strands. DnaB helicase is part of the larger replication fork machinery and interacts with several other proteins to initiate and continue DNA replication efficiently.

Function[edit | edit source]

DnaB helicase unwinds the DNA double helix at the replication fork. It operates by breaking the hydrogen bonds between the two DNA strands, allowing them to separate and serve as templates for replication. This enzyme is hexameric, meaning it consists of six identical subunits, which form a ring structure through which the DNA strand passes. The energy for the unwinding process is provided by the hydrolysis of ATP.

In addition to its helicase activity, DnaB interacts with other proteins involved in DNA replication. It forms a complex with the DnaC protein, which helps load the DnaB helicase onto the DNA. Once loaded, DnaB also interacts with the DNA polymerase and primase, facilitating the synthesis of the new DNA strands.

Mechanism[edit | edit source]

The mechanism of DnaB helicase involves the coordinated action of its six subunits. Each subunit alternately binds and hydrolyzes ATP, causing conformational changes in the protein that propel it along the DNA strand. This movement is directional, with DnaB typically moving in the 5' to 3' direction along the leading strand of DNA. As it moves, it unwinds the DNA ahead of it, creating single-stranded DNA templates for replication.

Regulation[edit | edit source]

The activity of DnaB helicase is tightly regulated to ensure that DNA replication occurs only at the right time and place within the cell. The loading of DnaB onto the DNA, for example, is controlled by the DnaC protein, which prevents premature unwinding of the DNA. Other proteins, such as the DnaA protein, are involved in the initial steps of replication initiation, ensuring that DnaB helicase is activated at the correct moment in the cell cycle.

Clinical Significance[edit | edit source]

Given its essential role in bacterial DNA replication, DnaB helicase is a target for the development of new antibacterial drugs. Inhibitors of DnaB helicase could potentially block bacterial DNA replication, leading to the death of the bacterial cell. This makes DnaB helicase an attractive target for antibacterial drug development, especially in the face of increasing antibiotic resistance.

Evolution[edit | edit source]

DnaB helicase is conserved across a wide range of bacteria, highlighting its fundamental role in DNA replication. However, the helicases involved in DNA replication in eukaryotes and archaea are different, although they perform a similar function. This evolutionary divergence reflects the different complexities and requirements of the replication machinery in these organisms.

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Contributors: Prab R. Tumpati, MD