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Literature summary for 2.7.6.5 extracted from

  • Hogg, T.; Mechold, U.; Malke, H.; Cashel, M.; Hilgenfeld, R.
    Conformational antagonism between opposing active sites in a bifunctional RelA/SpoT homolog modulates (p)ppGpp metabolism during the stringent response [corrected] (2004), Cell, 117, 57-68.
    View publication on PubMed

Application

Application Comment Organism
drug development the structural knowledge of the self-regulatory mechanisms for controlling the opposing catalytic activities of RelSeq can be used to design specific inhibitors that interfere with either of the active sites and may have the potential of being developped into powerful antibacterial drugs Streptococcus dysgalactiae

Cloned(Commentary)

Cloned (Comment) Organism
expression of the N-terminal catalytic fragment (residues 1-385) in Escherichia coli BL21 Streptococcus dysgalactiae

Crystallization (Commentary)

Crystallization (Comment) Organism
the crystallographic asymmetric unit contains two copies of RelSeq 1-385, two catalytic domains are clearly evident within each monomer, with the hydrolase (residues 5-159) and the synthetase (residues 176-371) domains joined by an overlapping central 3-helix bundle (residues 135-195) Streptococcus dysgalactiae

Protein Variants

Protein Variants Comment Organism
D264G eliminates detectable synthetase activity without appreciably altering the hydrolase activity Streptococcus dysgalactiae
E323Q eliminates detectable synthetase activity without appreciably altering the hydrolase activity Streptococcus dysgalactiae

Inhibitors

Inhibitors Comment Organism Structure
alpha,beta-methylene-ATP
-
Streptococcus dysgalactiae

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ essential for activation, the enzyme has a single Mg2+ binding site Streptococcus dysgalactiae
Mn2+ necessary cofactor at the hydrolase active site Streptococcus dysgalactiae

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + GTP Streptococcus dysgalactiae bifunctional enzyme with synthetase and hydrolase activities AMP + guanosine 5'-triphosphate 3'-diphosphate
-
r

Organism

Organism UniProt Comment Textmining
Streptococcus dysgalactiae
-
subsp. equisimilis
-

Purification (Commentary)

Purification (Comment) Organism
the catalytic fragment RelSeq 1-385 Streptococcus dysgalactiae

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + GTP bifunctional enzyme with synthetase and hydrolase activities Streptococcus dysgalactiae AMP + guanosine 5'-triphosphate 3'-diphosphate
-
r

Synonyms

Synonyms Comment Organism
Rel/Spo protein
-
Streptococcus dysgalactiae
RelSeq
-
Streptococcus dysgalactiae