InterPro domain: IPR014016

Helicases have been classified in 5 superfamilies (SF1-SF5). All of theproteins bind ATP and, consequently, all of them carry the classical Walker A(phosphate-binding loop or P-loop) and Walker B(Mg2+-binding aspartic acid) motifs. For the two largest groups, commonlyreferred to as SF1 and SF2, a total of seven characteristic motifs have beenidentified [ 1 ] which are distributed over two structural domains, anN-terminal ATP-binding domain and a C-terminal domain. UvrD-like DNA helicasesbelong to SF1, but they differ from classical SF1/SF2 by alarge insertion in each domain. UvrD-like DNA helicases unwind DNA with a3'-5' polarity [ 2 ].

Crystal structures of several uvrD-like DNA helicases have been solved [ 3 , 4 , 5 ]. They are monomeric enzymes consisting of twodomains with a common alpha-beta RecA-like core. The ATP-binding site issituated in a cleft between the N terminus of the ATP-binding domain and thebeginning of the C-terminal domain. The enzyme crystallizes in two differentconformations (open and closed). The conformational difference between the twoforms comprises a large rotation of the end of the C-terminal domain byapproximately 130 degrees. This "domain swiveling" was proposed to be an importantaspect of the mechanism of the enzyme [ 6 ].

Some proteins that belong to the UvrD-like DNA helicase family are listedbelow:

• 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'.

This domain is also found bacterial helicase-nuclease complex AddAB, both in subunit AddA and AddB. The AddA subunit is responsable for the helicase activity. AddB also harbors a putative ATP-binding domain which does not play a role as a secondary DNA motor, but that it may instead facilitate the recognition of the recombination hotspot sequences [ 6 ].

This entry represents the ATP-binding domain found in AddA, AddB and UvrD-like helicases.

1. Two related superfamilies of putative helicases involved in replication, recombination, repair and expression of DNA and RNA genomes. Nucleic Acids Res. 17, 4713-30
2. DNA helicases: 'inching forward'. Curr. Opin. Struct. Biol. 10, 124-8
3. Major domain swiveling revealed by the crystal structures of complexes of E. coli Rep helicase bound to single-stranded DNA and ADP. Cell 90, 635-47
4. Crystal structures of complexes of PcrA DNA helicase with a DNA substrate indicate an inchworm mechanism. Cell 97, 75-84
5. Crystal structure of RecBCD enzyme reveals a machine for processing DNA breaks. Nature 432, 187-93
6. The AddAB helicase-nuclease catalyses rapid and processive DNA unwinding using a single Superfamily 1A motor domain. Nucleic Acids Res. 39, 2271-85