The name of this superfamily has been modified since the most recent official CATH+ release (v4_2_0). At the point of the last release, this superfamily was: waiting to be named.
Family B DNA polymerases consist of five main structural domains: the N domain, the 3' - 5' Exo (exonuclease) domain, the palm domain, the finger domain and the thumb domain. The most conserved region includes a conserved tetrapeptide with two aspartate residues. Its function is not yet known, however, it has been suggested that it may be involved in binding a magnesium ion. All sequences in the B family contain a characteristic DTDS motif, and possess many functional domains, including a 5'-3' elongation domain, a 3'-5' exonuclease domain, a DNA binding domain, and binding domains for both dNTP's and pyrophosphate.
The catalytic core of DNA polymerase is formed from the thumb, palm and finger domains. It has a typical right-hand DNA polymerase fold, with an active site formed by a palm holding the catalytic residues, a thumb that binds the primer:template DNA and fingers interacting with incoming nucleotide, and the N and Exo domains extend from the finger toward the thumb. This superfamily entry represents the thumb domain found at the C-terminus of DNA polymerases B. Members of this superfamily include: DNA Polymerase alpha, delta, epsilon, zeta, DNA polymerase II (Pol II) in E. coli, yeast and Archaea. The most widely spread B-family polymerases are E. coli DNA pol II and eukaryotic pol zeta and are involved in translesion and mutagenic DNA synthesis.
Most interactions within the catalytic core domains are with the sugar-phosphate backbone, either directly, or via bridging water molecules. Not all of the residues are conserved throughout the B family polymerase sequences, but an overall channel of basic residues is maintained that stabilise the negatively charged phosphate groups. Lys 593 is within a highly conserved KKRY sequence motif in the thumb domain which is only found in the B family polymerases. It is thought that this KKRY motif stabilises the B form of DNA in RB69 (bacteriophage polymerase) by drawing the template and primer strands closer together.
The structure of Pol alpha bound to RNA primer/DNA template shows that, although the palm domain makes a canonical set of interactions with the first 3 bp of the primer-template helix, the thumb domain engages almost exclusively with the RNA primer strand. The interactions between the thumb domain and the RNA primer are concentrated in a contiguous region of five nucleotides, from position two to six of the RNA primer and involve solely the ribose and phosphate moieties of the RNA backbone. Two sequence motifs, residues 1074-1077 in the long segment of the L-shaped thumb, and residues 1130-1150 in the tip of the thumb, form a continuous protein interface that tracks the position of the phosphodiester backbone of the RNA primer. Pol alpha exploits the wide, shallow nature of the minor groove of the RNA/DNA helix with a series of hydrophobic contacts involving the side chains of Met1131, Leu1133, Tyr1140, Pro1141, Met1146, which recognise the C3'-endo conformation of the ribose moieties of RNA nucleotides in position four to six.
|Domain clusters (>95% seq id):||8|
|Domain clusters (>35% seq id):||7|
|Structural Clusters (5A):||1|
|Structural Clusters (9A):||1|