PROSITE documentation PDOC51198

UvrD-like DNA helicase domain profiles

Helicases have been classified in 5 superfamilies (SF1-SF5) [1]. All of the proteins bind ATP and, consequently, all of them carry the classical Walker A (phosphate-binding loop or P-loop) (see <PDOC00017>) and Walker B (Mg2+-binding aspartic acid) motifs [1]. For the two largest groups, commonly referred to as SF1 and SF2, a total of seven characteristic motifs have been identified [2] which are distributed over two structural domains, an N-terminal ATP-binding domain and a C-terminal domain. UvrD-like DNA helicases belong to SF1, but they differ from classical SF1/SF2 (see <PDOC51192>) by a large insertion in each domain. UvrD-like DNA helicases unwind DNA with a 3'-5' polarity [3].

Crystal structures of several uvrD-like DNA helicases have been solved (see for example <PDB:1UAA>) [4,5,6]. They are monomeric enzymes consisting of two domains with a common α-β RecA-like core. The ATP-binding site is situated in a cleft between the N-terminus of the ATP-binding domain and the beginning of the C-terminal domain. The enzyme crystallizes in two different conformations (open and closed). The conformational difference between the two forms comprises a large rotation of the end of the C-terminal domain by approximately 130 degrees. This "domain swiveling" was proposed to be an important aspect of the mechanism of the enzyme [5].

Some proteins that belong to the uvrD-like DNA helicase family are listed below:

• Bacterial UvrD helicase. It is involved in the post-incision events of nucleotide excision repair and methyl-directed mismatch repair. It unwinds DNA duplexes with 3'-5' polarity with respect to the bound strand and initiates unwinding most effectively when a single-stranded region is present.
• Gram-positive bacterial pcrA helicase, an essential enzyme involved in DNA repair and rolling circle replication. The Staphylococcus aureus pcrA helicase has both 5'-3' and 3'-5' helicase activities.
• Bacterial rep proteins, a single-stranded DNA-dependent ATPase involved in DNA replication which can initiate unwinding at a nick in the DNA. It binds to the single-stranded DNA and acts in a progressive fashion along the DNA in the 3' to 5' direction.
• Bacterial helicase IV (helD gene product). It catalyzes the unwinding of duplex DNA in the 3'-5' direction.
• Bacterial recB protein. RecBCD is a multi-functional enzyme complex that processes DNA ends resulting from a double-strand break. RecB is a helicase with a 3'-5' directionality.
• Fungal srs2 proteins, an ATP-dependent DNA helicase involved in DNA repair. The polarity of the helicase activity was determined to be 3'-5'.

To recognize uvrD-like DNA helicases we have developed two profiles. The first one recognizes the ATP-binding domain, whereas the second one is directed against the C-terminal domain.