{PDOC51199}
{PS51199; HELICASE_SF4}
{BEGIN}
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* Superfamily 4 helicase domain profile *
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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]. Superfamily 4 helicase, related to
bacterial  dnaB  proteins,  comprises  a  relatively  small  compact family of
proteins  containing,  in addition to Walker A and B, three distinct conserved
motifs  which  are  not  present  in  other  helicase  superfamilies. SF4 is a
hexameric  helicase  that  function  mainly  in bacterial or bacteriophage DNA
replication.   It   is  intimately  associated  with  other  proteins  of  the
replication fork. The helicase domain assembles into ring-shaped hexamers that
encircle  the  lagging  strand  of  the replication fork, moving in a 5' to 3'
direction and displacing the complementary DNA strand in an unwinding reaction
that is powered by nucleotide hydrolysis [2,3].

Several  bacteriophage  SF4  helicase  domains  have been crystalized (see for
example  <PDB:1CR0>)  [4].  The  central  core  is  similar  to the alpha-beta
RecA-like  domain. The functional enzyme is arranged in a ring-shaped hexamer.
A  nucleotide  binds in the crevice formed between adjacent subunits, where an
arginine  that  is analogous to the arginine finger motif of GTPase-activating
proteins  (see  <PDOC50238>)  could  trans-activate  the  bound nucleotide for
hydrolysis.  This  nucleotide-binding  site  at  the interface of two helicase
domains  is  also  a  feature  of  other DNA helicase such as PcrA, Rep or NS3
proteins, and it could be a general mechanism for DNA unwinding activity [4].

Some proteins known to contain an SF4 helicase domain are listed below [5,6]:

 - Bacterial  dnaB protein. It unwinds the DNA duplex ahead of the replication
   fork  and  is  also  responsible  for  attracting  the  dnaG primase to the
   replication fork.
 - Bacteriophage   T7  gp4  and  bacteriophage  T4  gp41  proteins.  They  are
   bifunctional  primase-helicases  that  unwind duplex DNA at the replication
   fork  while  initiating  the  synthesis of Okazaki fragments on the lagging
   strand.
 - Metazoan  Twinkle  proteins.  In  human, Twinkle  is a helicase involved in
   mitochondrial DNA replication. It has been implicated in autosomal dominant
   progressive  external  ophthalmoplegia  (adPEO),  a  mitochondrial disorder
   characterized by mtDNA deletions [7].
 - Several  Cryptophyta  and  Viridiplantae  hypothetical  proteins  that also
   contain a primase domain.
 - Several  protozoan hypothetical proteins that also contain a primase domain
   or an exonuclease domain.
 - Rhodophyta chloroplastic dnaB-like proteins.

The profile we developed covers the entire SF4 helicase domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: May 2006 / First entry.

[ 1] Gorbalenya A.E., and Koonin E.V. .
     "Helicases: amino acid sequence comparisons and structure-function
     relationships."
     Curr. Opin. Struct. Biol. 3:419-429(1993).
[ 2] LeBowitz J.H., McMacken R.
     "The Escherichia coli dnaB replication protein is a DNA helicase."
     J. Biol. Chem. 261:4738-4748(1986).
     PubMed=3007474
[ 3] Ahnert P., Patel S.S.
     "Asymmetric interactions of hexameric bacteriophage T7 DNA helicase
     with the 5'- and 3'-tails of the forked DNA substrate."
     J. Biol. Chem. 272:32267-32273(1997).
     PubMed=9405431
[ 4] Sawaya M.R., Guo S., Tabor S., Richardson C.C., Ellenberger T.
     "Crystal structure of the helicase domain from the replicative
     helicase-primase of bacteriophage T7."
     Cell 99:167-177(1999).
     PubMed=10535735
[ 5] Leipe D.D., Aravind L., Grishin N.V., Koonin E.V.
     "The bacterial replicative helicase DnaB evolved from a RecA
     duplication."
     Genome Res. 10:5-16(2000).
     PubMed=10645945
[ 6] Shutt T.E., Gray M.W.
     "Twinkle, the mitochondrial replicative DNA helicase, is widespread in
     the eukaryotic radiation and may also be the mitochondrial DNA primase
     in most eukaryotes."
     J. Mol. Evol. 62:588-599(2006).
     PubMed=16612544; DOI=10.1007/s00239-005-0162-8
[ 7] Spelbrink J.N., Li F.Y., Tiranti V., Nikali K., Yuan Q.P., Tariq M.,
     Wanrooij S., Garrido N., Comi G., Morandi L., Santoro L., Toscano A.,
     Fabrizi G.M., Somer H., Croxen R., Beeson D., Poulton J.,
     Suomalainen A., Jacobs H.T., Zeviani M., Larsson C.
     "Human mitochondrial DNA deletions associated with mutations in the
     gene encoding Twinkle, a phage T7 gene 4-like protein localized in
     mitochondria."
     Nat. Genet. 28:223-231(2001).
     PubMed=11431692; DOI=10.1038/90058

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