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Information on EC 5.5.1.16 - halimadienyl-diphosphate synthase
for references in articles please use BRENDA:EC5.5.1.16
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EC Tree 5 Isomerases
5.5 Intramolecular lyases
5.5.1 Intramolecular lyases (only sub-subclass identified to date)
5.5.1.16 halimadienyl-diphosphate synthase
IUBMB Comments
Requires Mg2+ for activity. This enzyme is found in pathogenic prokaryotes such as Mycobacterium tuberculosis but not in non-pathogens such as Mycobacterium smegmatis so may play a role in pathogenicity. The product of the reaction is subsequently dephosphorylated yielding tuberculosinol (halima-5,13-dien-15-ol).
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
showSynonyms
halimadienyl-diphosphate synthase, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CPS4:H501
-
H501D and H501F mutants of syncopalyl diphosphate synthase isoform CPS4
halimadienyl diphosphate synthase
HPS
Rv3377c
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
geranylgeranyl diphosphate = tuberculosinyl diphosphate
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
MetaCyc
1-tuberculosinyladenosine biosynthesis
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SYSTEMATIC NAME
IUBMB Comments
halima-5,13-dien-15-yl-diphosphate lyase (decyclizing)
Requires Mg2+ for activity. This enzyme is found in pathogenic prokaryotes such as Mycobacterium tuberculosis but not in non-pathogens such as Mycobacterium smegmatis so may play a role in pathogenicity. The product of the reaction is subsequently dephosphorylated yielding tuberculosinol (halima-5,13-dien-15-ol).
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
geranylgeranyl diphosphate
syn-halima-5,13E-dienyl diphosphate
-
Substrates: -
Products: -
Products: -
?
(E,E,E)-geranylgeranyl diphosphate
halimadienyl diphosphate
-
Substrates: -
Products: -
Products: -
?
(E,E,E)-geranylgeranyl diphosphate
halimadienyl diphosphate
-
Substrates: -
Products: -
Products: -
?
geranylgeranyl diphosphate
halima-5(6),13-dien-15-yl diphosphate
-
Substrates: -
Products: -
Products: -
?
geranylgeranyl diphosphate
halima-5(6),13-dien-15-yl diphosphate
-
Substrates: -
Products: -
Products: -
?
geranylgeranyl diphosphate
tuberculosinyl diphosphate
Substrates: -
Products: -
Products: -
?
geranylgeranyl diphosphate
tuberculosinyl diphosphate
Substrates: -
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
geranylgeranyl diphosphate
syn-halima-5,13E-dienyl diphosphate
-
Substrates: -
Products: -
Products: -
?
geranylgeranyl diphosphate
tuberculosinyl diphosphate
Substrates: -
Products: -
Products: -
?
geranylgeranyl diphosphate
tuberculosinyl diphosphate
Substrates: -
Products: -
Products: -
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Mg2+
-
the enzyme requires Mg2+ and reacts most efficiently in the presence of low levels (0.1 mM) of Mg2+
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Mg2+
-
the enzyme displays a rapid loss of activity as the Mg2+ concentration is raised above 0.1 mM
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000001
15-aza-14,15-dihydrogeranylgeranyl thiolodiphosphate
Mycobacterium tuberculosis
-
-
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
metabolism
-
class II diterpene cyclase that catalyzes the committed step in edaxadiene biosynthesis
metabolism
-
class II diterpene cyclase that catalyzes the committed step in edaxadiene biosynthesis
-
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). DITCY_MYCTU
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
501
0
55262
Swiss-Prot
-
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion method, using 20% (w/v) polyethylene glycol 8000 and 0.1 M CHES (pH 9.5) with 2 mM MgCl2
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A234N/F235V
the mutant predominantly produces tuberculosinyl diphosphate, with trace amounts of labda-8,13-dienyl diphosphate and labda-7,13-dienyl diphosphate from geranylgeranyl diphosphate
F171A
the mutant forms small amounts of tuberculosinyl diphosphate and labda-8,13-dienyl diphosphate, along with trace amounts of labda-7,13-dienyl diphosphate from geranylgeranyl diphosphate
F171H
the mutant generates significant amounts of copalyl diphosphate from geranylgeranyl diphosphate
F171H/A234N/F235V
the mutations lead to an almost complete loss of metabolic flux
Y328F
the mutant generates an alternative product (labda-7,13-dienyl diphosphate) from geranylgeranyl diphosphate
Y328F/Y479F
the mutant generates an alternative product (labda-7,13-dienyl diphosphate) from geranylgeranyl diphosphate
Y479F
the mutant generates an alternative product (labda-7,13-dienyl diphosphate) from geranylgeranyl diphosphate
F171H
-
the mutant generates significant amounts of copalyl diphosphate from geranylgeranyl diphosphate
-
Y328F
-
the mutant generates an alternative product (labda-7,13-dienyl diphosphate) from geranylgeranyl diphosphate
-
Y328F/Y479F
-
the mutant generates an alternative product (labda-7,13-dienyl diphosphate) from geranylgeranyl diphosphate
-
Y479F
-
the mutant generates an alternative product (labda-7,13-dienyl diphosphate) from geranylgeranyl diphosphate
-
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
-4
-
freezing leads to loss of about 10% activity over the course of 1 week
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4°C, less than 24 h, the enzyme retains essentially full activity
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Nakano, C.; Okamura, T.; Sato, T.; Dairi, T.; Hoshino, T.
Mycobacterium tuberculosis H37Rv3377c encodes the diterpene cyclase for producing the halimane skeleton
Chem. Commun. (Camb. )
28
1016-1018
2005
Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv3377c
brenda
Mann, F.M.; Prisic, S.; Hu, H.; Xu, M.; Coates, R.M.; Peters, R.J.
Characterization and inhibition of a class II diterpene cyclase from Mycobacterium tuberculosis: Implications for tuberculosis
J. Biol. Chem.
284
23574-23579
2009
Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv
brenda
Potter, K.C.; Jia, M.; Hong, Y.J.; Tantillo, D.; Peters, R.J.
Product rearrangement from altering a single residue in the rice syn-copalyl diphosphate synthase
Org. Lett.
18
1060-1063
2016
Oryza sativa
brenda
Lemke, C.; Roach, K.; Ortega, T.; Tantillo, D.J.; Siegel, J.B.; Peters, R.J.
Investigation of acid-base catalysis in halimadienyl diphosphate synthase involved in Mycobacterium tuberculosis virulence
ACS Bio Med Chem Au
2
490-498
2022
Mycobacterium tuberculosis (O50406), Mycobacterium tuberculosis H37Rv (O50406)
brenda
Zhang, Y.; Prach, L.M.; OBrien, T.E.; DiMaio, F.; Prigozhin, D.M.; Corn, J.E.; Alber, T.; Siegel, J.B.; Tantillo, D.J.
Crystal structure and mechanistic molecular modeling studies of Mycobacterium tuberculosis diterpene cyclase Rv3377c
Biochemistry
59
4507-4515
2020
Mycobacterium tuberculosis (O50406), Mycobacterium tuberculosis H37Rv (O50406)
brenda
EXTERNAL LINKS (specific for EC-Number 5.5.1.16)
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