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PDBsum entry 3nqw
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Contents |
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* Residue conservation analysis
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PDB id:
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Hydrolase
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Title:
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A metazoan ortholog of spot hydrolyzes ppgpp and plays a role in starvation responses
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Structure:
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Cg11900. Chain: a, b. Synonym: ip06614p, metazoan spot homolog 1, mesh1. Engineered: yes
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Source:
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Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Gene: cg11900, dmel_cg11900. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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2.90Å
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R-factor:
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0.213
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R-free:
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0.282
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Authors:
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D.W.Sun,H.Y.Kim,K.J.Kim,Y.H.Jeon,J.Chung
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Key ref:
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D.Sun
et al.
(2010).
A metazoan ortholog of SpoT hydrolyzes ppGpp and functions in starvation responses.
Nat Struct Biol,
17,
1188-1194.
PubMed id:
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Date:
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30-Jun-10
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Release date:
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08-Sep-10
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PROCHECK
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Headers
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References
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Q9VAM9
(MESH1_DROME) -
Guanosine-3',5'-bis(diphosphate) 3'-pyrophosphohydrolase MESH1 from Drosophila melanogaster
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Seq:
Struc:
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179 a.a.
178 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.3.1.7.2
- guanosine-3',5'-bis(diphosphate) 3'-diphosphatase.
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Reaction:
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guanosine 3',5'-bis(diphosphate) + H2O = GDP + diphosphate + H+
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guanosine 3',5'-bis(diphosphate)
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+
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H2O
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=
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GDP
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+
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diphosphate
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+
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H(+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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Nat Struct Biol
17:1188-1194
(2010)
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PubMed id:
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A metazoan ortholog of SpoT hydrolyzes ppGpp and functions in starvation responses.
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D.Sun,
G.Lee,
J.H.Lee,
H.Y.Kim,
H.W.Rhee,
S.Y.Park,
K.J.Kim,
Y.Kim,
B.Y.Kim,
J.I.Hong,
C.Park,
H.E.Choy,
J.H.Kim,
Y.H.Jeon,
J.Chung.
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ABSTRACT
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In nutrient-starved bacteria, RelA and SpoT proteins have key roles in reducing
cell growth and overcoming stresses. Here we identify functional SpoT orthologs
in metazoa (named Mesh1, encoded by HDDC3 in human and Q9VAM9 in Drosophila
melanogaster) and reveal their structures and functions. Like the bacterial
enzyme, Mesh1 proteins contain an active site for ppGpp hydrolysis and a
conserved His-Asp-box motif for Mn(2+) binding. Consistent with these structural
data, Mesh1 efficiently catalyzes hydrolysis of guanosine 3',5'-diphosphate
(ppGpp) both in vitro and in vivo. Mesh1 also suppresses SpoT-deficient
lethality and RelA-induced delayed cell growth in bacteria. Notably, deletion of
Mesh1 (Q9VAM9) in Drosophila induces retarded body growth and impaired
starvation resistance. Microarray analyses reveal that the amino acid-starved
Mesh1 null mutant has highly downregulated DNA and protein synthesis-related
genes and upregulated stress-responsible genes. These data suggest that metazoan
SpoT orthologs have an evolutionarily conserved function in starvation responses.
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Links
