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PDBsum entry 7oa2
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References listed in PDB file
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Key reference
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Title
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The archaeal triphosphate tunnel metalloenzyme sattm defines structural determinants for the diverse activities in the cyth protein family.
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Authors
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M.S.Vogt,
R.R.Ngouoko nguepbeu,
M.K.F.Mohr,
S.V.Albers,
L.O.Essen,
A.Banerjee.
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Ref.
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J Biol Chem, 2021,
297,
100820.
[DOI no: ]
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PubMed id
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Abstract
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CYTH proteins make up a large superfamily that is conserved in all three domains
of life. These enzymes have a triphosphate tunnel metalloenzyme (TTM) fold,
which typically results in phosphatase functions, e.g., RNA triphosphatase,
inorganic polyphosphatase, or thiamine triphosphatase. Some CYTH orthologs
cyclize nucleotide triphosphates to 3',5'-cyclic nucleotides. So far, archaeal
CYTH proteins have been annotated as adenylyl cyclases, although experimental
evidence to support these annotations is lacking. To address this gap, we
characterized a CYTH ortholog, SaTTM, from the crenarchaeote Sulfolobus
acidocaldarius. Our in silico studies derived ten major subclasses within the
CYTH family implying a close relationship between these archaeal CYTH enzymes
and class IV adenylyl cyclases. However, initial biochemical characterization
reveals inability of SaTTM to produce any cyclic nucleotides. Instead, our
structural and functional analyses show a classical TTM behavior, i.e.,
triphosphatase activity, where pyrophosphate causes product inhibition. The
Ca2+-inhibited Michaelis complex indicates a two-metal-ion reaction
mechanism analogous to other TTMs. Cocrystal structures of SaTTM further reveal
conformational dynamics in SaTTM that suggest feedback inhibition in TTMs due to
tunnel closure in the product state. These structural insights combined with
further sequence similarity network-based in silico analyses provide a firm
molecular basis for distinguishing CYTH orthologs with phosphatase activities
from class IV adenylyl cyclases.
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Secondary reference #1
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Title
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The archaeal triphosphate tunnel metalloenzyme sa ttm defines structural determinants for the diverse activ in the cyth protein family
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Authors
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M.S.Vogt,
R.R.N.Nguepbeu,
M.K.F.Mohr,
S.V.Albers,
L.O.Essa.Banerjee.
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Ref.
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biorxiv ...
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