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Synonyms
chorismate mutase, p-protein, chorismate mutase/prephenate dehydratase, chorismate mutase-prephenate dehydrogenase, bacillus subtilis chorismate mutase, cm type 2, cm0819, atcm1, rv1885c, chorismate mutase 1,
more
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chlorogenic acid
CGA, a structural analogue of chorismic acid, is an inhibitor of chorismate mutase, type II regulatory domain (BsCM_2). It binds to BsCM_2 with a higher affinity than chorismate. Similar to BsCM_2, in BsAroH, the chlorogenic acid's position is shifted from the transition state analogue position. The chlorogenic acid interacts with residues Arg63, Val73, Thr74 from one chain and Arg7, Arg90, Val114, Leu115, and Arg116 from the adjacent chain
oxabicyclic dicarboxylic acid
transition state analogon, competitive inhibition
(1R,3R,5S)-3-carboxy-1-hydroxy-2-oxabicyclo[3.3.1]non-6-ene-5-carboxylate
-
-
(1S,3R,5R)-1-hydroxy-5-nitro-2-oxabicyclo[3.3.1]non-6-ene-3-carboxylic acid
-
-
(1S,3S,5R)-1-hydroxy-5-nitro-2-oxabicyclo[3.3.1]non-6-ene-3-carboxylic acid
-
-
chlorogenic acid
CGA, a structural analogue of chorismic acid, is an inhibitor of chorismate mutase, type II regulatory domain (BsCM_2). It binds to BsCM_2 with a higher affinity than chorismate. The BsCM_2-CGA structure has several residues in alternate conformations. His73 exists as alternative conformation in both the chains. At active site S1, the chlorogenic acid makes hydrogen bonds with the side chain of Arg27, Lys38, Gln86, and the main chain atoms of Arg45, Asp47, and Phe79 of chain B. The ligand molecule also interacts with Lys38, Arg50, and Lys80 of chain B, and Arg10 of chain A through water bridge formation. However, at active site S2, along with the above interactions, the ligand forms a direct hydrogen bond with Lys80 and an additional water bridge-mediated hydrogen bond with Gln86 of chain A
chorismate
-
strain WB672, inhibition above 2 mM
additional information
the similarity of chlorogenic acid's interaction with both monofunctional chorismate mutases BsAroH and BsCM_2 may result in similar binding to both proteins
-
additional information
the similarity of chlorogenic acid's interaction with both monofunctional chorismate mutases BsAroH and BsCM_2 may result in similar binding to both proteins
-
additional information
-
the similarity of chlorogenic acid's interaction with both monofunctional chorismate mutases BsAroH and BsCM_2 may result in similar binding to both proteins
-
additional information
the similarity of chlorogenic acid's interaction with both monofunctional chorismate mutases BsAroH and BsCM_2 may result in similar binding to both proteins
-
additional information
the similarity of chlorogenic acid's interaction with both monofunctional chorismate mutases BsAroH and BsCM_2 may result in similar binding to both proteins
-
additional information
-
the similarity of chlorogenic acid's interaction with both monofunctional chorismate mutases BsAroH and BsCM_2 may result in similar binding to both proteins
-
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additional information
additional information
-
0.067
chorismate
30°C, pH 7, wild-type
0.067
chorismate
pH 7.5, 37°C, recombinant AroH
0.15
chorismate
30°C, pH 7, mutant R90G
1.9
chorismate
30°C, pH 7, mutant C88K/R90S
4.3
chorismate
30°C, pH 7, mutant C88S/R90K
0.074
chorismate
-
wild-type
0.081
chorismate
-
30°C, pH 7.5, wild-type, with 4 mM substrate
1
chorismate
-
strain WB672
1.514
chorismate
pH 7.5, 37°C, recombinant BsCM_2
2.6
chorismate
-
strain 168
3.9
chorismate
-
30°C, pH 7.5, mutant DELTA118-127, with 5.8 mM substrate
4
chorismate
-
30°C, pH 7.5, mutant DELTA119-127/D118N, with 5.8 mM substrate
4.1
chorismate
-
30°C, pH 7.5, mutant DELTA118-127, with 3.4 mM substrate
9.3
chorismate
-
30°C, pH 7.5, mutant DELTA117-127, with 3.8 mM substrate
9.6
chorismate
-
DELTA 117-127
15
chorismate
-
30°C, pH 7.5, mutant DELTA118-127/K111N/A112S/V113N, with 4 mM substrate
16
chorismate
-
30°C, pH 7.5, mutant DELTA118-127/R116L/P117T, with 3.9 mM substrate
additional information
additional information
Michaelis-Menten kinetics
-
additional information
additional information
Michaelis-Menten kinetics
-
additional information
additional information
-
Michaelis-Menten kinetics
-
additional information
additional information
Michaelis-Menten kinetics
-
additional information
additional information
Michaelis-Menten kinetics
-
additional information
additional information
-
Michaelis-Menten kinetics
-
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additional information
additional information
-
0.0003
chorismate
30°C, pH 7, mutant R90G
0.29
chorismate
30°C, pH 7, mutant C88S/R90K
0.32
chorismate
30°C, pH 7, mutant C88K/R90S
46
chorismate
30°C, pH 7, wild-type
46
chorismate
pH 7.5, 37°C, recombinant AroH
0.78
chorismate
pH 7.5, 37°C, recombinant BsCM_2
2 - 8
chorismate
-
mutant DELTA117-127
22
chorismate
-
30°C, pH 7.5, mutant DELTA118-127, with 5.8 mM substrate
23
chorismate
-
30°C, pH 7.5, mutant DELTA119-127/D118N, with 5.8 mM substrate
24
chorismate
-
30°C, pH 7.5, mutant DELTA118-127, with 3.4 mM substrate
26
chorismate
-
30°C, pH 7.5, mutant DELTA117-127, with 3.8 mM substrate and DELTA 118-127/R116L/P117T, with 3.9 mM substrate
30
chorismate
-
30°C, pH 7.5, mutant DELTA118-127/K111N/A112S/V113N, with 4 mM substrate
41
chorismate
-
wild-type
47
chorismate
-
30°C, pH 7.5, wild-type, with 4 mM substrate
additional information
additional information
R90Cit 10E4-fold decrease in the catalytic activity of kcat. R90K 10E4-fold decrease in the catalytic activity of kcat/Km is obtained
-
additional information
additional information
-
R90Cit 10E4-fold decrease in the catalytic activity of kcat. R90K 10E4-fold decrease in the catalytic activity of kcat/Km is obtained
-
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0.003 - 1.1
oxabicyclic dicarboxylic acid
0.001 - 0.051
(1R,3R,5S)-3-carboxy-1-hydroxy-2-oxabicyclo[3.3.1]non-6-ene-5-carboxylate
0.00032 - 0.0029
(1S,3R,5R)-1-hydroxy-5-nitro-2-oxabicyclo[3.3.1]non-6-ene-3-carboxylic acid
0.23
(1S,3S,5R)-1-hydroxy-5-nitro-2-oxabicyclo[3.3.1]non-6-ene-3-carboxylic acid
-
30°C, pH 7.5, wild-type
additional information
oxabicyclic dicarboxylic acid
0.003
oxabicyclic dicarboxylic acid
30°C, pH 7, wild-type
0.004
oxabicyclic dicarboxylic acid
30°C, pH 7, mutant R90G
1.1
oxabicyclic dicarboxylic acid
30°C, pH 7, mutant C88K/R90S
0.001
(1R,3R,5S)-3-carboxy-1-hydroxy-2-oxabicyclo[3.3.1]non-6-ene-5-carboxylate
-
30°C, pH 7.5, wild-type
0.051
(1R,3R,5S)-3-carboxy-1-hydroxy-2-oxabicyclo[3.3.1]non-6-ene-5-carboxylate
-
30°C, pH 7.5, mutant DELTA117-127
0.00032
(1S,3R,5R)-1-hydroxy-5-nitro-2-oxabicyclo[3.3.1]non-6-ene-3-carboxylic acid
-
30°C, pH 7.5, wild-type
0.0029
(1S,3R,5R)-1-hydroxy-5-nitro-2-oxabicyclo[3.3.1]non-6-ene-3-carboxylic acid
-
30°C, pH 7.5, mutant DELTA117-127
additional information
oxabicyclic dicarboxylic acid
>> 1 mM mutant C88S/R90K
additional information
oxabicyclic dicarboxylic acid
-
>> 1 mM mutant C88S/R90K
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evolution
the N-terminal domain of DAHPS from Bacillus subtilis is homologous to the AroQ class of chorismate mutase, type II. Bacillus subtilis also contains a monofunctional AroH class of chorismate mutase situated downstream of the shikimate pathway
malfunction
mutant Arg90Cit, a sluggish variant of Bacillus subtilis chorismate mutase, in which a cationic active-site arginine is replaced by a neutral citrulline, is a poor catalyst even though it effectively preorganizes chorismate for the reaction
evolution
the N-terminal domain of DAHPS from Bacillus subtilis is homologous to the AroQ class of chorismate mutase, type II. Bacillus subtilis also contains a monofunctional AroH class of chorismate mutase situated downstream of the shikimate pathway
physiological function
in Bacillus subtilis, the N-terminal domain of the bifunctional 3-deoxy-D-arabino-heptulosonate-7-phosphate-synthase (DAHPS), the first enzyme of the shikimate pathway, belongs to an AroQ class of chorismate mutase and is functionally homologous to the downstream AroH class chorismate mutase. BsCM_2 has a regulatory function in the bifunctional DAHPS enzyme, regulation of DAHPS enzyme activity by the CM2 domain, overview
physiological function
in Bacillus subtilis, the N-terminal domain of the bifunctional 3-deoxy-D-arabino-heptulosonate-7-phosphate-synthase (DAHPS), the first enzyme of the shikimate pathway, belongs to an AroQ class of chorismate mutase and is functionally homologous to the downstream AroH class chorismate mutase. BsCM_2 may also have a regulatory function in the bifunctional DAHPS enzyme
physiological function
the enzyme catalyzes the rearrangement of chorismate to prephenate. Calculations have predicted the decisive factor in chorismate mutase catalysis to be ground state destabilization rather than transition state stabilization
additional information
AroH molecular docking, using crystal structure of BsAroH, PDB ID 2CHT, overview
additional information
AroH molecular docking, using crystal structure of BsAroH, PDB ID 2CHT, overview
additional information
-
AroH molecular docking, using crystal structure of BsAroH, PDB ID 2CHT, overview
additional information
structural basis of ligand binding into the active site of AroQ class of chorismate mutase from crystal structure analysis, conformational flexibility of active site loop, overview. Molecular dynamics results show that helix H2' undergoes uncoiling at the first turn and increases the mobility of loop L1'. The side chains of Arg45, Phe46, Arg52 and Lys76 undergo conformational changes, which may play an important role in DAHPS regulation by the formation of the domain-domain interface. BsCM_2 active site architecture and its regulatory role, molecular dynamics simulation, overview
additional information
structural basis of ligand binding into the active site of AroQ class of chorismate mutase from crystal structure analysis, conformational flexibility of active site loop, overview. Molecular dynamics results show that helix H2' undergoes uncoiling at the first turn and increases the mobility of loop L1'. The side chains of Arg45, Phe46, Arg52 and Lys76 undergo conformational changes, which may play an important role in DAHPS regulation by the formation of the domain-domain interface. BsCM_2 active site architecture and its regulatory role, molecular dynamics simulation, overview
additional information
-
structural basis of ligand binding into the active site of AroQ class of chorismate mutase from crystal structure analysis, conformational flexibility of active site loop, overview. Molecular dynamics results show that helix H2' undergoes uncoiling at the first turn and increases the mobility of loop L1'. The side chains of Arg45, Phe46, Arg52 and Lys76 undergo conformational changes, which may play an important role in DAHPS regulation by the formation of the domain-domain interface. BsCM_2 active site architecture and its regulatory role, molecular dynamics simulation, overview
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crystal structures of double mutants C88S/R90K and C88K/R90S, hanging drop vapour diffusion method at room temperature, space group R3 with a and b: 82.6 A and c: 42.8 A
hanging drop vapor-diffusion method at room temperature and high ionic strength, orthorhombic space group P212121 with a: 52.2 A, b: 83.8 A, c: 86.0 A, nine sulfate ions, five glycerol molecules, 424 water molecules
Performance of molecular dynamics simulations for the three enzyme-ligand complexes(CHOR,PRE and TSA) in addition to the TPS calculations. 8-hydroxy-2-oxa-bicyclo[3.3.1]non-6-ene-3,5-dicarboxylic acid as a TSA. The principal component analysis (PCA) to analyze structures is used
purified recombinant wild-type enzyme, hanging drop vapor diffusion technique, mixing of 0.001 ml of 3 mM protein in 10 mM Tris buffer, pH 7.5, 2 mM DTT, and 0.125 mM EDTA with 0.001 ml of reservoir solution containing 100 mM malic acid, Mes, Tris (MMT buffer) (in molar ratios of 1:2:2, respectively), pH 6.0, 100-150 mM MgCl2, 25% w/v PEG 1000, and 0.3 mM NaN3, at 20°C, 4-5 days, X-ray diffraction structure determination and analysis at resolution at 1.59 A resolution, molecular replacement using crystal structure PDB ID 1DBF as search model. Purified recombinant mutant enzyme Arg90Cit free or complexed with either substrate, product, or a transition state analogue, hanging drop vapor diffusion technique, mixing of 750 nl of 3 mM protein in 20 mM Tris, pH 8.0, 0.6 mM PMSF, 0.3 mM NaN3 with 750 nl of reservoir solution 100 mM MMT buffer pH 6.0, 50-150 mM CaCl2, 24-26% w/v PEG 1000, and 0.3 mM NaN3, at 20°C, 3-4 days, X-ray diffraction structure determination and analysis at resolution at 1.61-1.80 A resolution, modeling
purified recombinant enzyme AroQ (BsCM_2) in complex with citrate and chlorogenic acid, sitting drop vapor diffusion method, mixing of 0.001 ml of 18 mg/ml protein in 25 mM Tris-HCl, pH 7.5, and 50 mM NaCl, with 0.001 ml of reservoir solution containing 1 M ammonium sulphate, 0.1 M potassium sodium tartrate, and 0.1 M sodium citrate, pH 5.8, 20°C, 15 days, X-ray diffraction structure determination and analysis at 1.9 A and 1.8 A resolution, respectively, molecular replacement using the structure of the N-terminal CM domain of bifunctional DAHPS from Listeria monocytogens (PDB ID 3NVT) as template
structure of N-terminal domain AroQ in complex with citrate and chlorogenic acid at 1.9 A and 1.8 A resolution, respectively. Helix H2' undergoes uncoiling at the first turn and increases the mobility of loop L1'. The side chains of Arg45, Phe46, Arg52 and Lys76 undergo conformational changes, which may play an important role in DAHPS regulation by the formation of the domain-domain interface. Chlorogenic acid binds with a higher affinity than chorismate
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C88K/R90S
lower activity than wild-type enzyme
C88S/R90K
lower activity than wild-type enzyme
R90A
no activity detectable
R90K
The ES, TS, and product structures of the mutants are determined based on the wild-type structure. The hydrogen-bond lengths of the mutants differ from the wild-type. The two mutants chemical reaction progresses in a similar way. No large geometrical changes in and around the active site along the reaction path: only a small rearrangement of the hydrogen-bond sites. As for Lys90/Cit90 mutant reactions, no large conformational change is observed in the overall protein structure except for the geometries around the mutation point. Although the catalytic activity of R90K is inferior to that of the wild-type, the enzymatic mechanism of the R90K mutant is similar to the wild-type. The main anticatalytic factor of R90Cit mutant is the ES stabilization as a result of destabilizing the substrate by the surrounding electrostatic field because of the mutated enzyme. Therefore the TS stabilization mechanism of the Cit90 mutant is quite different from that of the wild-type BsCM
C75S
-
viscosity-insensitive
DELTA118-127
-
large increase in KM and slower turnover relative to wild-type enzyme
DELTA118-127/K111N/A112S/V113N
-
large increase in KM and slower turnover relative to wild-type enzyme
DELTA118-127/R116L/P117T
-
large increase in KM and slower turnover relative to wild-type enzyme
DELTA119-127/D118N
-
large increase in KM and slower turnover relative to wild-type enzyme
R90Q
-
complete inactivation of enzyme
DELTA117-127
-
large increase in KM and slower turnover relative to wild-type enzyme
DELTA117-127
-
lower turnover and lower KM than wild-type enzyme
additional information
mutant Arg90Cit, a sluggish variant of Bacillus subtilis chorismate mutase, in which a cationic active-site arginine is replaced by a neutral citrulline, is a poor catalyst even though it effectively preorganizes chorismate for the reaction
additional information
-
mutant Arg90Cit, a sluggish variant of Bacillus subtilis chorismate mutase, in which a cationic active-site arginine is replaced by a neutral citrulline, is a poor catalyst even though it effectively preorganizes chorismate for the reaction
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Lorence, J.H.; Nester, E.W.
Multiple molecular forms of chorismate mutase in Bacillus subtilis
Biochemistry
6
1541-1553
1967
Bacillus subtilis, Bacillus subtilis 23
brenda
Gray, J.V.; Golinelli-Pimpaneau, B.; Knowles, J.R.
Monofunctional chorismate mutase from Bacillus subtilis: purification of the protein, molecular cloning of the gene, and overexpression of the gene product in Escherichia coli
Biochemistry
29
376-383
1990
Bacillus subtilis
brenda
Ladner, J.E.; Reddy, P.; Davis, A.; Tordova, M.; Howard, A.J.; Gilliland, G.L.
The 1.30 A resolution structure of the Bacillus subtilis chorismate mutase catalytic homotrimer
Acta Crystallogr. Sect. D
56
673-683
2000
Bacillus subtilis (P19080)
-
brenda
Gamper, M.; Hilvert, D.; Kast, P.
Probing the role of the C-terminus of Bacillus subtilis chorismate mutase by a novel random protein-termination strategy
Biochemistry
39
14087-14094
2000
Bacillus subtilis
brenda
Mandal, A.; Hilvert, D.
Charge optimization increases the potency and selectivity of a chorismate mutase inhibitor
J. Am. Chem. Soc.
125
5598-5599
2003
Bacillus subtilis, Escherichia coli
brenda
Marti, S.; Andres, J.; Moliner, V.; Silla, E.; Tunon, I.; Bertran, J.
A comparative study of claisen and cope rearrangements catalyzed by chorismate mutase. An insight into enzymatic efficiency: transition state stabilization or substrate preorganization?
J. Am. Chem. Soc.
126
311-319
2004
Bacillus subtilis
brenda
Kast, P.; Grisostomi, C.; Chen, I.A.; Li, S.; Krengel, U.; Xue, Y.; Hilvert, D.
A strategically positioned cation is crucial for efficient catalysis by chorismate mutase
J. Biol. Chem.
275
36832-36838
2000
Bacillus subtilis (P19080), Bacillus subtilis
brenda
Ranaghan, K.E.; Mulholland, A.J.
Conformational effects in enzyme catalysis: QM/MM free energy calculation of the 'NAC' contribution in chorismate mutase
Chem. Commun. (Camb.)
2004
1238-1239
2004
Bacillus subtilis
-
brenda
Szefczyk, B.; Mulholland, A.J.; Ranaghan, K.E.; Sokalski, W.A.
Differential transition-state stabilization in enzyme catalysis: quantum chemical analysis of interactions in the chorismate mutase reaction and prediction of the optimal catalytic field
J. Am. Chem. Soc.
126
16148-16159
2004
Bacillus subtilis
brenda
Marti, S.; Moliner, V.; Tunon, I.; Williams, I.H.
Computing kinetic isotope effects for chorismate mutase with high accuracy. A new DFT/MM strategy
J. Phys. Chem. B
109
3707-3710
2005
Bacillus subtilis
brenda
Ishida, T.; Fedorov, D.G.; Kitaura, K.
All electron quantum chemical calculation of the entire enzyme system confirms a collective catalytic device in the chorismate mutase reaction
J. Phys. Chem. B
110
1457-1463
2006
Bacillus subtilis (P19080), Bacillus subtilis
brenda
Crehuet, R.; Field, M.J.
A transition path sampling study of the reaction catalyzed by the enzyme chorismate mutase
J. Phys. Chem. B
111
5708-5718
2007
Bacillus subtilis (P19080)
brenda
Ishida, T.
Effects of point mutation on enzymatic activity: Correlation between protein electronic structure and motion in chorismate mutase reaction
J. Am. Chem. Soc.
132
7104-7118
2010
Bacillus subtilis (P19080)
brenda
Claeyssens, F.; Ranaghan, K.E.; Lawan, N.; Macrae, S.J.; Manby, F.R.; Harvey, J.N.; Mulholland, A.J.
Analysis of chorismate mutase catalysis by QM/MM modelling of enzyme-catalysed and uncatalysed reactions
Org. Biomol. Chem.
9
1578-1590
2011
Bacillus subtilis
brenda
Burschowsky, D.; van Eerde, A.; Oekvist, M.; Kienhoefer, A.; Kast, P.; Hilvert, D.; Krengel, U.
Electrostatic transition state stabilization rather than reactant destabilization provides the chemical basis for efficient chorismate mutase catalysis
Proc. Natl. Acad. Sci. USA
111
17516-17521
2014
Bacillus subtilis (P19080), Bacillus subtilis
brenda
Pratap, S.; Dev, A.; Kumar, V.; Yadav, R.; Narwal, M.; Tomar, S.; Kumar, P.
Structure of chorismate mutase-like domain of DAHPS from Bacillus subtilis complexed with novel inhibitor reveals conformational plasticity of active site
Sci. Rep.
7
6364
2017
Bacillus subtilis (P19080), Bacillus subtilis (P39912), Bacillus subtilis, Bacillus subtilis 168 (P19080), Bacillus subtilis 168 (P39912)
brenda