Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 4.6.1.1 extracted from

  • Findeisen, F.; Linder, J.U.; Schultz, A.; Schultz, J.E.; Bruegger, B.; Wieland, F.; Sinning, I.; Tews, I.
    The structure of the regulatory domain of the adenylyl cyclase Rv1264 from Mycobacterium tuberculosis with bound oleic acid (2007), J. Mol. Biol., 369, 1282-1295.
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
additional information regulatory domain of Rv1264 regulates AC activity in a pH-dependent manner, activated at acidic pH due to pH-dependent structural transitions of the Rv1264 dimer, strongly activated by the addition of fatty acids, oleic acid may serve as a hinge Mycobacterium tuberculosis

Cloned(Commentary)

Cloned (Comment) Organism
overexpression of the histidine-tagged auto-inhibitory domain Rv1264N in Escherichia coli BL21(DE3)[pREP4] cells Mycobacterium tuberculosis

Crystallization (Commentary)

Crystallization (Comment) Organism
by the hanging-drop, vapour-diffusion method at 18°C, to 1.6 A resolution, crystal structure of the histidine-tagged auto-inhibitory domain Rv1264N shows the protein in a tight, disk-shaped dimer, formed around a helical bundle, and involving a protein chain crossover Mycobacterium tuberculosis

Protein Variants

Protein Variants Comment Organism
E136A shift of the pH optimum by about 0.5 unit to acidic pH Mycobacterium tuberculosis
E136R shift of the pH optimum by about 0.5 unit to acidic pH Mycobacterium tuberculosis
H103A pH regulation is barely affected, not involved in pH-regulation Mycobacterium tuberculosis
H140A pH regulation is barely affected, not involved in pH-regulation, shift of the pH optimum by about 0.5 unit to acidic pH Mycobacterium tuberculosis
H140R inhibition is relaxed slightly, with a shift of the pH optimum toward more basic values Mycobacterium tuberculosis
H58A pH regulation is barely affected, not involved in pH-regulation Mycobacterium tuberculosis
additional information deletion in the shoulder domain of the holoenzyme, linking of the two adjoining Calpha positions of residues Ala93 and His103, which are 4.6 A apart, mutant enzyme is 7fold more active at pH 8.0 compared to the wild-type enzyme, and shows only a residual 3fold activation at pH 5.5. When the entire shoulder domain is deleted, residues Asp62 to Arg105, the phenotype is similar. This deletion joins the Calpha positions of residues Gly61 and Ala106, which are 6.4 A apart in the wild-type structure Mycobacterium tuberculosis
R132A shift of the pH optimum by about 0.5 unit to acidic pH Mycobacterium tuberculosis
R132E results in a biphasic pH activity curve with a minimum at pH 6.5 and higher activity at basic pH values Mycobacterium tuberculosis

Inhibitors

Inhibitors Comment Organism Structure
additional information addition of one or two residues results in a slightly more inhibited phenotype. Addition of three residues results in only subtle changes, probably because the insertion of three residues is compatible with an extra-helical turn. In contrast, insertion of nine amino acids almost abolishes pH sensitivity Mycobacterium tuberculosis

Metals/Ions

Metals/Ions Comment Organism Structure
Mn2+
-
Mycobacterium tuberculosis

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
45000
-
histidine-tagged auto-inhibitory domain Rv1264N, gel filtration Mycobacterium tuberculosis

Organism

Organism UniProt Comment Textmining
Mycobacterium tuberculosis P9WQ35
-
-
Mycobacterium tuberculosis H37Rv P9WQ35
-
-

Purification (Commentary)

Purification (Comment) Organism
histidine-tagged auto-inhibitory domain Rv1264N, on nickel nitrilotriacetic acid/agarose column, to purity Mycobacterium tuberculosis

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP
-
Mycobacterium tuberculosis 3',5'-cAMP + diphosphate
-
?
ATP
-
Mycobacterium tuberculosis H37Rv 3',5'-cAMP + diphosphate
-
?

Subunits

Subunits Comment Organism
dimer histidine-tagged auto-inhibitory domain Rv1264N, gel filtration Mycobacterium tuberculosis

Synonyms

Synonyms Comment Organism
class III AC
-
Mycobacterium tuberculosis
Rv1264
-
Mycobacterium tuberculosis

pH Range

pH Minimum pH Maximum Comment Organism
5 8
-
Mycobacterium tuberculosis