Helicases structure

Caruthers, J. M. and McKay, D. B. Helicase structure and mechanism. Curr. Opin. Struct. Biol. 12 123-133, 2002. 

Figure 27.16. Helicase Structure. The bacterial helicase PcrA comprises four domains Al, A2, Bl, and B2. The A1 domain includes a P-loop NTPase fold, whereas the Bl domain has a similar overall structure but lacks a P-loop and does not bind nucleotides. Single-stranded DNA binds to the Al and Bl domains near the interfaces with domains A2 and B2.

K. J. Marians. 2000. Crawling and wiggling on DNA Structural insights to the mechanism of DNA unwinding by helicases Structure FoldDes. 5 R227-R235. 

The N-terminal domain of yeast eIF4A is structurally similar to RecA, two DNA helicases (Per and Rep), and the RNA helicase NS3 from hepatitis C virus. Despite differences in amino acid sequence and substrate specificity, these domains share a common fold involved in ATP hydrolysis (Bird et al., 1998). The domains have a core structure composed of five parallel (3-strands connected by a-helices within an a/p motif. In eIF4A, the helicase core consists of -strands S2, S3, and S5-S7 and a-helices H4, H5, and H7-H9. In most extant helicase structures, polypeptide regions flanking the core have either additional secondary structure elements or entire domains that are specific to the biochemical functions to these related molecules. The core domain establishes a scaffold upon which residues involved in ATP binding and hydrolysis are located (motifs I, la, II, and III). 

Heat of combustion, 113 Heat of hydrogenation, 186 table of, 187 Heat of reaction, 154 Helicase, DNA replication and, 1106 Hell-Volhard-Zelinskii reaction, 849 amino acid synthesis and. 1025 mechanism of, 849 Heme, biosynthesis of, 966 structure of, 946 Hemiacetal, 717 Hemiketal, 717 Hemithioacetal, 1148 Henderson-Hasselbalch equation,... 

One exciting approach is the development of short sequences of RNA that bind specifically to HCV helicase and/or the protease activity found in the same hepatitis C virus-encoded non-structural protein, NS3, and inhibit helicase at sub-micromolar concenttations (Umehara et al. 2005). These molecules could provide the basis for developing potent helicase inhibitors with improved pharmacotherapeutic properties. 

Examples (a) nucleosome K Huger, AW Mader, RK Richmond, DF Sargent, TJ Richmond. Nature 389 251-260, 1997 (b) DNA polymerases CA Brautigam, TA Steitz. Curr. Opin. Struct. Biol. 8 54-63, 1998 (c) single-stranded binding protein Y Shamoo, AM Friedman, MR Parsons, WH Konigsberg, TA Steitz. Nature 376 362-366, 1995 (d) restriction endonucleases RA Kovall, BW Matthews. Curr. Opin. Chem. Biol. 3 578-583, 1999 (e) DNA lig-ase S Shuman. Structure 4 653-656, 1996 (f) DNA helicases MC Hall, SW Matson. Mol. Microbiol. 34 867-877, 1999 (g) zinc-finger proteins Y Choo, JW Schwabe. Nat. Struct. Biol. 5 253-255, 1998. 

Fig. 2.2 (A) Structure of full-length NS3 including the N-terminal protease domain (bottom) and C-terminal helicase domain (top). The NS4A peptide (purple) is covalently attached to the N-terminus of NS3 (see text). Within the protease domain the N- and C-terminal -barrels are at the right and left, respectively. The zinc atom is visible at the bottom left. [98]. (B) Surface view of the NS3 protease domain showing compound (1) bound at the relatively shallow active site (See also Fig. 2.6) [42].

Helicases catalyze the processive separation of duplex DNA into single strands. Despite sharing similarity to helicases, none of the chromatin remodelling factors, with the exception of the INO80 complex, have been shown to catalyze the separation of DNA strands (Shen et al, 2000). Instead, they can translocate on double-stranded (ds) DNA in an ATP-hydrolysis dependent manner and are characterized by their ability to generate superhelical torsional strain in DNA (Havas et al, 2000 Saha et al, 2002 Whitehouse et al, 2003). The crystal structure of Rad54, a member of the SWI/SNF family has been solved for both S. solfataricus and zebrafish which helps to understand the mechanism of the SWI/SNF ATPase domain in remodelling processes (Durr et al, 2005 Thoma et al, 2005). It reveals... 

Travers, A.A. (1992) The reprogramming of transcriptional competence. Cell 69, 573-575. Velankar, S.S., Soultanas, P., Dillingham, M.S., Subramanya, H.S., and Wigley, D.B. (1999) Crystal structures of complexes of PcrA DNA helicase with a DNA substrate indicate an inch-worm mechanism. Cell 97, 75-84. 

The vulnerable point for insulin-mediated regulation of translation is the initiation factor eIF-4E. This factor binds specifically to the 5 -cap structure of mRNA and is part of a larger complex, termed eIF-4F. A further component of eIF-4F is the eIF-4A protein, which possesses helicase activity. The binding of eIF-4E to the cap structure is necessary for the association of the 40S subunit with the 5 -end of the mRNA and for... 

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