Book Summary:
Structural bioinformatics, the branch of bioinformatics that refers to three-dimensional macromolecular structures, utilizes various computational tools to infer protein function, establish evolutionary relationships, determine shape and electrostatic properties of proteins, etc. Structural bioinformatics was used to analyze the fingers subdomain of various DNA polymerase families, enzymes essential to DNA replication. The DNA polymerases have structures that resemble a half-opened right hand, and therefore, their three major subdomains are named as the palm, thumb and fingers. Although the fingers subdomain is conserved among families, they vary considerably across families. Y-family DNA polymerases, the newly classified group of DNA polymerases, are highly error prone and have the ability to bypass DNA lesions and thereby replicate past a damaged template. The structural data show that these enzymes contain the classic palm, fingers, and thumb subdomains, characteristic of all DNA polymerases. In addition, they contain an extra domain referred to as 'little fingers' or 'polymerase-associated domain (PAD).' Although a few suggestions have been made, the function of this domain has yet to be defined. In order to gain insight into the function of this domain, a structural bioinformatics approach was used. The PAD domain of Dpo4 Y-family DNA polymerases (Sulfolobus sulfataricus , residues 244-341) was subjected to search structural homologues using DALI. One hundred and sixty one proteins were identified with structural homology. Of these, only sixty-three proteins were further studied as they contained the complete structural unit of the PAD (β,α,β,β,α,β) or at a minimum, one α helix and three β strands. The rest of the proteins contained only partial homology with the PAD and therefore, were discarded. Superimposition of the sixty-three proteins further implied that thirty-three proteins had significant structural homology. This significant structural homology was defined as a core structure consisting of one α helix and three β strands. Nineteen of the 33 proteins (58%) identified belonged to a group of proteins involved in transfer activity. Sequence alignments derived from the structural data showed conservation of hydrophobic residues between α helices and β strands suggesting the requirement of these residues for the maintenance of the core structure. (Abstract shortened by UMI.) |