Evidence map›Paper›PMID 19317511›Full record

ArticleBiochemistry2009

Mutational analysis of Mycobacterium UvrD1 identifies functional groups required for ATP hydrolysis, DNA unwinding, and chemomechanical coupling.

Krishna Murari Sinha, Michael S Glickman, Stewart Shuman

Open access · greenAbstract read
In one paragraph

Article in Biochemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.7field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 35 citations in OpenAlex.

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  4. Proceedings of the National Academy of Sciences of the United States of America · 2022
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  11. The SF1 helicase encoded by the archaeal plasmid pTN2 of Thermococcus nautili.Extremophiles : life under extreme conditions · 2014
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Krishna Murari SinhaMolecular Biology Program, Sloan-Kettering Institute, New York, New York 10021, USA.
Michael S Glickman
Stewart Shuman
Kettering University · USMemorial Sloan Kettering Cancer Center · US

Funding

Novel pathway of DNA inter-strand crosslink repair in mycobacteriaR01AI064693 · NIAID · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Michael S Glickman, Stewart H Shuman · 2005 to 2026
$11.1M
CD4 T Cell Responses to M. Tuberculosis InfectionR01AI080619 · NIAID · SLOAN-KETTERING INST CAN RESEARCH · PI GLICKMAN, MICHAEL S, PAMER, ERIC G. · 2009 to 2013
$2.3M
NIAID NIH HHS AI64693NIAID NIH HHS R01 AI064693NIAID NIH HHS R01 AI080619
6 · The paper itself

Abstract

Mycobacterial UvrD1 is a DNA-dependent ATPase and a Ku-dependent 3' to 5' DNA helicase. The UvrD1 motor domain resembles that of the prototypal superfamily I helicases UvrD and PcrA. Here we performed a mutational analysis of UvrD1 guided by the crystal structure of a DNA-bound Escherichia coli UvrD-ADP-MgF(3) transition state mimetic. Alanine scanning and conservative substitutions identified amino acids essential for both ATP hydrolysis and duplex unwinding, including those implicated in phosphohydrolase chemistry via transition state stabilization (Arg308, Arg648, Gln275), divalent cation coordination (Glu236), or activation of the nucleophilic water (Glu236, Gln275). Other residues important for ATPase/helicase activity include Phe280 and Phe72, which interact with the DNA 3' single strand tail. ATP hydrolysis was uncoupled from duplex unwinding by mutations at Glu609 (in helicase motif V), which contacts the ATP ribose sugar. Introducing alanine in lieu of the adenine-binding "Q motif" glutamine (Gln24) relaxed the substrate specificity in NTP hydrolysis, e.g., eliciting a gain of function as a UTPase/TTPase, although the Q24A mutant still relied on ATP/dATP for duplex unwinding. Our studies highlight the role of the Q motif as a substrate filter and the contributions of adenosine-binding residues as couplers of NTP hydrolysis to motor activity. The Ku-binding function of UvrD1 lies within its C-terminal 270 amino acid segment. Here we found that deleting the 90 amino acid C-terminal domain, which is structurally uncharacterized, diminished DNA unwinding, without affecting ATP hydrolysis or binding to the DNA helicase substrate, apparently by affecting the strength of the UvrD1-Ku interaction.

Indexed as

Adenosine TriphosphatasesAdenosine TriphosphateAlanineAmino Acid MotifsAmino Acid SequenceAmino Acid SubstitutionBacterial ProteinsBinding SitesConserved SequenceDNA HelicasesDNA Mutational AnalysisDNA RepairDNA, Single-StrandedEscherichia coliEscherichia coli ProteinsHydrolysisAdenosine TriphosphatasesAdenosine TriphosphateAlanineBacterial ProteinsDNA HelicasesDNA, Single-StrandedEscherichia coli Proteins

Identifiers

PMID19317511
PMCPMC2761027
OpenAlexW2051169186

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.