The arginine finger of bacteriophage T7 gene 4 helicase: Role in energy coupling

Crampton, Donald J.; Guo, S.Y.; Johnson, Donald E.; Richardson, Charles C.

doi:10.1073/pnas.0400968101

Cited by 55 publications

(51 citation statements)

References 47 publications

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“…For example, with one defective cylinder, the machine may continue to operate with the remaining five. In the case of T7gp4, DNA-dependent ATPase activity has been shown to require an active catalytic base (E343) at all six subunit interfaces [66 ], but some inactive arginine fingers are permitted [87]. The most direct studies of a multisubunit machine's tolerance to individual ATP site disruption involve the bacterial unfoldase ClpX [79 ].…”

Section: Tolerance To Atp Site Disruptionmentioning

confidence: 99%

On helicases and other motor proteins

Enemark

Joshua‐Tor

2008

Current Opinion in Structural Biology

192

238

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Helicases are molecular machines that utilize energy derived from ATP hydrolysis to move along nucleic acids and to separate base-paired nucleotides. The movement of the helicase can also be described as a stationary helicase that pumps nucleic acid. Recent structural data for the hexameric E1 helicase of papillomavirus in complex with single-stranded DNA and MgADP has provided a detailed atomic and mechanistic picture of its ATP-driven DNA translocation. The structural and mechanistic features of this helicase are compared with the hexameric helicase prototypes T7gp4 and SV40 T-antigen. The ATP-binding site architectures of these proteins are structurally similar to the sites of other prototypical ATP-driven motors such as F1-ATPase, suggesting related roles for the individual site residues in the ATPase activity. IntroductionHelicases are essential enzymes that unwind duplex DNA, RNA, or DNA-RNA hybrids. This unwinding is driven by consumption of input energy that is harnessed to separate base-paired oligonucleotides and also to maintain a unidirectional advancement of the helicase upon the nucleic acid substrate. This translocation can alternatively be described as an immobile helicase pumping nucleic acid. The energy for these transformations is derived from the hydrolysis of nucleotide triphosphate (NTP). Helicases can be depicted as an internal combustion engine with each individual NTPase site serving as one cylinder. Each individual cylinder follows a defined series of events: injection (ATP binding), compression (optimally positioning the site for hydrolysis), combustion (ATP hydrolysis/work generation), and exhaust (ADP and phosphate release). In a helicase, the individual combustion cylinders coordinate these actions to carry out the repetitive mechanical operation of prying open base pairs and/or actively translocating with respect to the nucleic acid substrate. Many other molecular motors utilize similar engines to carry out multiple diverse functions such as translocation of peptides in the case of ClpX, movement along cellular structures in the case of dyenin, and rotation about an axle as in F 1 -ATPase.Based upon conserved sequence motifs, helicases have been classified into six superfamilies [1,2 ]. An extensive review of these superfamilies has been provided recently [3 ]. Superfamily 1 (SF1) and superfamily 2 (SF2) helicases are very prevalent, generally monomeric, and participate in several diverse DNA and RNA manipulations. The other helicase superfamilies form hexameric rings (reviewed in [4]), as demonstrated by biochemistry [5][6][7][8] and electron microscopy studies [9][10][11][12][13][14][15][16][17], and often participate at the replication fork. All of these helicases bind and hydrolyze NTP at the interface between two recA-like domains. The binding site consists of a Walker A (P-loop) and a Walker B motif from the first domain and other elements such as an arginine finger from the other domain. The SF1 and SF2 helicases contain two recAlike domains coupled by a short linker, and t...

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Section: Tolerance To Atp Site Disruptionmentioning

confidence: 99%

On helicases and other motor proteins

Enemark

Joshua‐Tor

2008

Current Opinion in Structural Biology

192

238

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“…The Arg-finger points from a second RecA-like domain that is adjacent to the domain containing the P-loop and provides a positive charge that stabilizes the transition state [128,129]. In ring helicases the Argfinger and P-loop are part of different polypeptide chains in the hexamer [130], explaining why ring helicases need to oligomerize in order to catalyze a reaction. In non-ring helicases the Arg-finger is part of the C-terminal RecA-like domain while the P-loop is on the Nterminal RecA-like domain.…”

Section: Helicase Structure and Functionmentioning

confidence: 99%

Understanding Helicases as a Means of Virus Control

Frick¹,

Lam²

2006

CPD

103

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Helicases are promising antiviral drug targets because their enzymatic activities are essential for viral genome replication, transcription, and translation. Numerous potent inhibitors of helicases encoded by herpes simplex virus, severe acute respiratory syndrome coronavirus, hepatitis C virus, Japanese encephalitis virus, West Nile virus, and human papillomavirus have been recently reported in the scientific literature. Some inhibitors have also been shown to decrease viral replication in cell culture and animal models. This review discusses recent progress in understanding the structure and function of viral helicases to help clarify how these potential antiviral compounds function and to facilitate the design of better inhibitors. The above helicases and all related viral proteins are classified here based on their evolutionary and functional similarities, and the key mechanistic features of each group are noted. All helicases share a common motor function fueled by ATP hydrolysis, but differ in exactly how the motor moves the protein and its cargo on a nucleic acid chain. The helicase inhibitors discussed here influence rates of helicase-catalyzed DNA (or RNA) unwinding by preventing ATP hydrolysis, nucleic acid binding, nucleic acid release, or by disrupting the interaction of a helicase with a required cofactor.

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“…The majority of each pocket is formed by one CTD, whereas the adjacent CTD provides an arginine residue, the arginine finger, whose guanadinium group contacts the g-phosphate of the bound NTP. The arginine finger is believed to stimulate NTP hydrolysis and to help modulate the relative orientation of the CTDs in response to NTP hydrolysis (18,24).…”

mentioning

confidence: 99%

Structure of Hexameric DnaB Helicase and Its Complex with a Domain of DnaG Primase

Bailey

Eliason

Steitz

2007

Science

194

301

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The complex between the DnaB helicase and the DnaG primase unwinds duplex DNA at the eubacterial replication fork and synthesizes the Okazaki RNA primers. The crystal structures of hexameric DnaB and its complex with the helicase binding domain (HBD) of DnaG reveal that within the hexamer the two domains of DnaB pack with strikingly different symmetries to form a distinct two-layered ring structure. Each of three bound HBDs stabilizes the DnaB hexamer in a conformation that may increase its processivity. Three positive, conserved electrostatic patches on the N-terminal domain of DnaB may also serve as a binding site for DNA and thereby guide the DNA to a DnaG active site.

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The arginine finger of bacteriophage T7 gene 4 helicase: Role in energy coupling

Cited by 55 publications

References 47 publications

On helicases and other motor proteins

On helicases and other motor proteins

Understanding Helicases as a Means of Virus Control

Structure of Hexameric DnaB Helicase and Its Complex with a Domain of DnaG Primase

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