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Information on EC 3.5.4.19 - phosphoribosyl-AMP cyclohydrolase
for references in articles please use BRENDA:EC3.5.4.19
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EC Tree 3 Hydrolases
3.5 Acting on carbon-nitrogen bonds, other than peptide bonds
3.5.4 In cyclic amidines
3.5.4.19 phosphoribosyl-AMP cyclohydrolase
IUBMB Comments
The Neurospora crassa enzyme also catalyses the reactions of EC 1.1.1.23 (histidinol dehydrogenase) and EC 3.6.1.31 (phosphoribosyl-ATP diphosphatase).
The enzyme appears in viruses and cellular organisms
- 3.5.4.19
- hi
- vannielii
-
phosphoribosyl-atp
-
methanobacterium
-
methanococcus
-
metalloenzyme
- purine
- thermoautotrophicum
- drug development
Reaction Schemes
showSynonyms
pr-amp cyclohydrolase, phosphoribosyl-amp cyclohydrolase, pra-ch, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
HisI
N1-(5'-phosphoribosyl) adenosine-5'-monophosphate cyclohydrolase
-
phosphoribosyladenosine monophosphate cyclohydrolase
-
-
-
-
PR-AMP cyclohydrolase
PRA-CH
-
-
-
-
PRAMP-cyclohydrolase
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
1-(5-phospho-beta-D-ribosyl)-AMP + H2O = 1-(5-phospho-beta-D-ribosyl)-5-[(5-phospho-beta-D-ribosylamino)methylideneamino]imidazole-4-carboxamide
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of N-C-binding
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
BRENDA
MetaCyc
L-histidine biosynthesis
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SYSTEMATIC NAME
IUBMB Comments
1-(5-phospho-D-ribosyl)-AMP 1,6-hydrolase
The Neurospora crassa enzyme also catalyses the reactions of EC 1.1.1.23 (histidinol dehydrogenase) and EC 3.6.1.31 (phosphoribosyl-ATP diphosphatase).
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CAS REGISTRY NUMBER
COMMENTARY
37289-22-8
-
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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
1-(5-phospho-beta-D-ribosyl)-AMP + H2O
1-(5-phospho-beta-D-ribosyl)-5-[(5-phospho-beta-D-ribosylamino)methylideneamino]imidazole-4-carboxamide
Substrates: -
Products: -
Products: -
?
1-(5-phosphoribosyl)-AMP + H2O
1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino]imidazole-4-carboxamide
1-(5-phosphoribosyl)-AMP + H2O
1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino]imidazole-4-carboxamide
Substrates: -
Products: -
Products: -
?
1-(5-phosphoribosyl)-AMP + H2O
1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino]imidazole-4-carboxamide
-
Substrates: -
Products: -
Products: -
?
1-(5-phosphoribosyl)-AMP + H2O
1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino]imidazole-4-carboxamide
-
Substrates: -
Products: -
Products: -
ir
1-(5-phosphoribosyl)-AMP + H2O
1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino]imidazole-4-carboxamide
-
Substrates: the enzyme is involved in histidine biosynthesis
Products: -
Products: -
ir
1-(5-phosphoribosyl)-AMP + H2O
1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino]imidazole-4-carboxamide
-
Substrates: -
Products: -
Products: -
?
1-(5-phosphoribosyl)-AMP + H2O
1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino]imidazole-4-carboxamide
-
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
1-(5-phosphoribosyl)-AMP + H2O
1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino]imidazole-4-carboxamide
1-(5-phosphoribosyl)-AMP + H2O
1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino]imidazole-4-carboxamide
Substrates: -
Products: -
Products: -
?
1-(5-phosphoribosyl)-AMP + H2O
1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino]imidazole-4-carboxamide
-
Substrates: -
Products: -
Products: -
?
1-(5-phosphoribosyl)-AMP + H2O
1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino]imidazole-4-carboxamide
-
Substrates: the enzyme is involved in histidine biosynthesis
Products: -
Products: -
ir
1-(5-phosphoribosyl)-AMP + H2O
1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino]imidazole-4-carboxamide
-
Substrates: -
Products: -
Products: -
?
1-(5-phosphoribosyl)-AMP + H2O
1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino]imidazole-4-carboxamide
-
Substrates: -
Products: -
Products: -
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Cd2+
-
0.95 Cd2+ per enzyme subunit, competes with and replaces Zn2+, binding affects the enzyme structure, three Cd2+ are coordinated by residues Asp85 and Cys86 from one monomer and Cys109 from the other monomer, the fourth Cd2+ is bound by His16 and Asp89
Mg2+
required for cataltic activity. The C93 reactivity is modulated by the presence of the Zn2+ and Mg2+ and substantiates the role of this residue as a metal ligand
Zn2+
Zn2+
metalloprotein. The Zn2+ coordination site involves the three conserved cysteine residues. The C93 reactivity is modulated by the presence of the Zn2+ and Mg2+ and substantiates the role of this residue as a metal ligand
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5,5'-dithiobis(2-nitrobenzoic acid)
compromises the Zn2+ binding properties of the protein inducing loss of up to 90% of the metal. The enzyme is protected from inactivation by inclusion of the substrate N1-(5'-phosphoribosyl)adenosine 5'-monophosphate, while Mg2+, a metal required for catalytic activity, enhanced the rate of inactivation
methyl methane thiosulfonate
compromises the Zn2+ binding properties of the protein inducing loss of up to 90% of the metal
additional information
ZINC04880153 can be considered as one of the potential lead molecule against HisI drug target in Brucella melitensis. Low binding energy (-9.1kcal/mol) with a molecular weight of 228.191 g/mol. It has 2 H-bond donors and 7 H-bond acceptors. The movement of ZINC04880153 in the binding pockets of HisI shows stability and compact structure with respect to the initial computational model of HisI
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
steady-state kinetics of the enzyme with bound Zn2+ or with Cd2+ bound at different pH, recombinant enzyme, overview
-
0.18
1-(5-phospho-beta-D-ribosyl)-AMP
mutant enzyme D94E, pH and temperature not specified in the publication
0.83
1-(5-phospho-beta-D-ribosyl)-AMP
mutant enzyme H110A, pH and temperature not specified in the publication
2.3
1-(5-phospho-beta-D-ribosyl)-AMP
mutant enzyme D92E, pH and temperature not specified in the publication
4 - 10
1-(5-phospho-beta-D-ribosyl)-AMP
wild-type enzyme, pH and temperature not specified in the publication
0.00075
1-(5-phosphoribosyl)-AMP
-
pH 8.0, 65°C, recombinant enzyme with bound Cd2+
0.0009
1-(5-phosphoribosyl)-AMP
-
pH 8.5, 65°C, recombinant enzyme with bound Cd2+
0.0136
1-(5-phosphoribosyl)-AMP
-
pH 8.0, 65°C, recombinant enzyme with bound Zn2+
0.0204
1-(5-phosphoribosyl)-AMP
-
pH 8.5, 65°C, recombinant enzyme with bound Zn2+
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.28
1-(5-phosphoribosyl)-AMP
-
pH 8.5, 65°C, recombinant enzyme with bound Cd2+
0.29
1-(5-phosphoribosyl)-AMP
-
pH 8.0, 65°C, recombinant enzyme with bound Cd2+
6.4
1-(5-phosphoribosyl)-AMP
-
pH 8.0, 65°C, recombinant enzyme with bound Zn2+
9.9
1-(5-phosphoribosyl)-AMP
-
pH 8.5, 65°C, recombinant enzyme with bound Zn2+
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
physiological function
the enzyme catalyzes the third step of histidine biosynthesis
metabolism
the enzyme is involved in many important pathways such as biosynthesis of amino acids
metabolism
Brucella melitensis bv. 1 ATCC 23456
-
the enzyme is involved in many important pathways such as biosynthesis of amino acids
-
Show AA Sequence and Transmembrane Helices (36161 entries)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
tetramer
-
the cytoplasmic C-terminus harbors the active site for the histidinol dehydrogenase, EC 1.1.1.23, activity
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified untagged recombinant enzyme, hanging drop vapour diffusion method, 2 mg/ml protein in 50 mM Tris-HCl, pH 7.5, is mixed in a 1:1 ratio with reservoir solution containing 100 mM HEPES-HCl, pH 7.5, 50 mM CdSO4, 1.6 M sodium acetate, and 10% w/v glycerol, X-ray diffraction structure determination and analysis at 1.7 A resolution
-
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C109/C116
no measurable catalytic activity, not capable of binding Zn2+
C109A
no measurable catalytic activity, not capable of binding Zn2+
C116A
no measurable catalytic activity, still capable of binding Zn2+
D92E
180fold loss in catalytic efficiency (kcat/Km), decrease in Zn2+ content
D94A
no measurable catalytic activity, decrease in Zn2+ content
H110A
500fold decrease in activity, no decrease in Zn2+ content
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme from Escherichia coli by anion exchange chromatography and dialysis
-
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of the enzyme in Escherichia coli strains MC1061 and BL21(DE3), the His-tagged enzyme constantly shows aggregation after expression
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
drug development
the enzyme is identified as drug target. Brucella melitensis is a pathogenic gram-negative bacterium which is known for causing zoonotic diseases (Brucellosis). The organism is highly contagious and is used as bioterrorism agent against humans
drug development
Brucella melitensis bv. 1 ATCC 23456
-
the enzyme is identified as drug target. Brucella melitensis is a pathogenic gram-negative bacterium which is known for causing zoonotic diseases (Brucellosis). The organism is highly contagious and is used as bioterrorism agent against humans
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Keesey, J.K.; Bigelis, R.; Fink, G.R.
The product of the his4 gene cluster in Saccharomyces cerevisiae. A trifunctional polypeptide
J. Biol. Chem.
254
7427-7433
1979
Saccharomyces cerevisiae
brenda
Fujimori, K.; Ohta, D.
Isolation and characterization of a histidine biosynthetic gene in Arabidopsis encoding a polypeptide with two separate domains for phosphoribosyl-ATP pyrophosphohydrolase and phosphoribosyl-AMP cyclohydrolase
Plant Physiol.
118
275-283
1998
Arabidopsis thaliana (O82768)
brenda
Minson, A.C.; Creaser, E.H.
Purification of a trifunctional enzyme, catalysing three steps of the histidine pathway, from Neurospora crassa
Biochem. J.
114
49-56
1969
Neurospora crassa
brenda
DOrdine, R.L.; Klem, T.J.; Davisson, V.J.
N1-(5'-phosphoribosyl)adenosine-5'-monophosphate cyclohydrolase: purification and characterization of a unique metalloenzyme
Biochemistry
38
1537-1546
1999
Methanococcus vannielii
brenda
Sivaraman, J.; Myers, R.S.; Boju, L.; Sulea, T.; Cygler, M.; Jo Davisson, V.; Schrag, J.D.
Crystal structure of Methanobacterium thermoautotrophicum phosphoribosyl-AMP cyclohydrolase HisI
Biochemistry
44
10071-10080
2005
Methanothermobacter thermautotrophicus
brenda
D'Ordine, R.L.; Linger, R.S.; Thai, C.J.; Davisson, V.J.
Catalytic zinc site and mechanism of the metalloenzyme PR-AMP cyclohydrolase
Biochemistry
51
5791-5803
2012
Methanococcus vannielii (Q50837), Methanococcus vannielii
brenda
Gupta, M.; Prasad, Y.; Sharma, S.K.; Jain, C.K.
Identification of phosphoribosyl-AMP cyclohydrolase, as drug target and its inhibitors in Brucella melitensis bv. 1 16M using metabolic pathway analysis
J. Biomol. Struct. Dyn.
35
287-299
2017
Brucella melitensis bv. 1 (Q8YH95), Brucella melitensis bv. 1 ATCC 23456 (Q8YH95)
brenda
EXTERNAL LINKS (specific for EC-Number 3.5.4.19)
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Release 2023.1 (January 2023)
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