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Enzyme Nomenclature
Information on EC 5.1.1.4 - proline racemase
for references in articles please use BRENDA:EC5.1.1.4
Word Map on EC 5.1.1.4
- 5.1.1.4
- trypanosoma
- cruzi
- d-proline
- chagas
-
oversaturated
- vivax
- diaminopimelate
-
pyrrole-2-carboxylic
-
stickland
-
pracs
-
abeles
-
ethiopia
-
2-epimerase
- congolense
-
stereoinversion
-
trypanosomosis
- medicine
- drug development
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The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
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EC NUMBER 
COMMENTARY 
5.1.1.4
-
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RECOMMENDED NAME
GeneOntology No.
proline racemase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
L-proline = D-proline
-
-
-
-
L-proline = D-proline
racemization is accompanied by deuterium incorporation from the solvent into the alpha position of Pro, participation of two equivalent hydrogen acceptor sites
-
L-proline = D-proline
two-base mechanism in which one base on the enzyme removes the substrate alpha-hydrogen as a proton and the conjugate acid of another base donates a proton to the opposite side of the alpha-carbon
-
L-proline = D-proline
energetics of proline racemase: transition-state fractionation factors for the two protons involved in the catalytic steps
-
L-proline = D-proline
stepwise reaction for the interconversion of the free enzyme forms in which a proton is abstracted from a bound water molecule to give a reaction intermediate having a hydroxide ion bound to the diprotonated form of the enzyme
-
L-proline = D-proline
enzyme exists in two states, one of which binds and isomerizes L-Pro and the other of which binds and isomerizes D-Pro. It seems likely that the two enzyme forms differ only in the protonation states of the acidic and basic groups at the active site
-
L-proline = D-proline
fractionation factors for the essential catalytic groups in the enzyme-substrate complexes
-
L-proline = D-proline
mechanism is best accomodated by a route that involves a transition state or unstable intermediate in which the proline carbanion is flanked by the two catalytic thiols of the enzyme
-
L-proline = D-proline
the substrate and product 'on-off' steps are faster than the racemization step and the racemization reaction proceeds either in a concerted manner or in a stepwise fashion involving enzyme catalytic groups, e.g. thiols
-
L-proline = D-proline
a new combined quantum mechanical and molecular mechanical (QM/MM) potential to study the reaction mechanism of proline racemase is used. Three critical points are identified: two almost isoenergetic minima (M1a and M2a), in which the enzyme is bound to L- and D-Pro, respectively, and a transition state (TSCa), unveiling a highly asynchronous concerted process; quantum mechanical and molecular mechanical study reveals two almost isoenergetic minima M1a and M2a, in which the enzyme is bound to L-proline and D-proline, respectively, and a transition state TSCa, unveiling a highly asynchronous concerted process. Residues Asn133, Asp296, and Gly301 destabilize M2a. Conversely, both Gly131and Gly303 stabilize M2a. Residues Gly131, Gly301, and Thr302 stabilize TSCa
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
racemization
racemization
-
-
-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
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SYSTEMATIC NAME
IUBMB Comments
proline racemase
-
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CAS REGISTRY NUMBER
COMMENTARY
9024-09-3
-
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
catalyzes step 8 in the ornithine fermentation pathway
physiological function
physiological function
-
proline racemase is an effective mitogen for B cells, thus contributing to the parasites immune evasion and persistence in the human host
physiological function
proline racemase participates in mechanisms of virulence acquisition; proline racemase participates in mechanisms of virulence acquisition
physiological function
enzyme is a T-cell-independent B-cell mitogen, enzyme displays mitogenic activity towards splenic cells from euthymic Swiss mice, since addition of 0.1 mg/ml of recombinant protein promotes a 13fold increase of thymidine incorporation when compared with untreated cells, mitogenic activity of recombinant enzyme seems to be dependent on the active enzyme, since inhibition with 10 mM pyrrole-2-carboxylic acid prior to its incubation with splenocytes specifically decreases proliferation by 44%, enzyme triggers high levels of B-cell activation, terminal differentiation and antibody secretion
physiological function
-
proline racemase is a T-cell-independent B-cell mitogen, stimulation of murine splenocytes with recombinant proline racemase C induces B-cell proliferation, antibody secretion, interleukin-10 production, and upregulation of CD69 and CD86 on B cells
physiological function
-
inactivation of proline racemase PrdF by insertional mutagenesis does not affect early logarithmic growth but only attenuates growth in the mid- and late logarithmic phases. There is no effect of inactivation on virulence in vivo
physiological function
-
proline racemase is a T-cell-independent B-cell mitogen, stimulation of murine splenocytes with recombinant proline racemase C induces B-cell proliferation, antibody secretion, interleukin-10 production, and upregulation of CD69 and CD86 on B cells
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
D-proline
L-proline
H3ZMH5
the reaction is completely bi-directional, and the reverse reactions. The specific activity with D-proline is 130% compared to the L-enantiomer. The bifunctional enzyme reversibly catalyzes the racemization of proline and the epimerization of 4-hydroxyproline and 3-hydroxyproline with similar kinetic constants. Catalysis is based on the same 1,1-proton transfer mechanism using two general acidic/basic cysteine residues located on opposite faces of the active site
-
-
?
D-proline
L-proline
H3ZMH5
the reaction is completely bi-directional, and the reverse reactions. The specific activity with D-proline is 130% compared to the L-enantiomer. The bifunctional enzyme reversibly catalyzes the racemization of proline and the epimerization of 4-hydroxyproline and 3-hydroxyproline with similar kinetic constants. Catalysis is based on the same 1,1-proton transfer mechanism using two general acidic/basic cysteine residues located on opposite faces of the active site
-
-
?
L-azetidine-2-carboxylate
D-azetidine-2-carboxylate
H3ZMH5
low activity
-
-
?
L-azetidine-2-carboxylate
D-azetidine-2-carboxylate
H3ZMH5
low activity
-
-
?
L-Pro
D-Pro
-
overexpression of TcPRAC leads to an increase in parasite differentiation into infective forms and its subsequent penetration into host cells. During infection of its mammalian host, the parasite secretes a proline racemase that contributes to parasite immune evasion by acting as a B-cell mitogen
-
-
?
L-proline
D-proline
-
two-base racemization mechanism via an aci-carboxylate intermediate
-
-
r
L-proline
D-proline
CdPRAC from Clostridium difficile racemizes both L- and D-Pro but not OH-L/D-Pro or any other natural amino acid
-
-
r
L-proline
D-proline
CdPRAC from Clostridium difficile racemizes both L- and D-Pro but not OH-L/D-Pro or any other natural amino acid
-
-
r
L-proline
D-proline
kcat/Km value for trans-4-hydroxy-L-proline is about 3fold lower than that for L-proline, which is attributed to a 17fold lower kcat value. The kinetic parameters of the epimerization of cis-4-hydroxy-D-proline can not be determined
-
-
r
L-proline
D-proline
the enzyme can utilize both proline and hydroxyprolines as substrate
-
-
r
L-proline
D-proline
the enzyme can utilize both proline and hydroxyprolines as substrate
-
-
r
L-proline
D-proline
H3ZMH5
the reaction is completely bi-directional, and the reverse reactions. The specific activity with D-proline is 130% compared to the L-enantiomer. The bifunctional enzyme reversibly catalyzes the racemization of proline and the epimerization of 4-hydroxyproline and 3-hydroxyproline with similar kinetic constants. Catalysis is based on the same 1,1-proton transfer mechanism using two general acidic/basic cysteine residues located on opposite faces of the active site
-
-
r
L-proline
D-proline
H3ZMH5
the reaction is completely bi-directional, and the reverse reactions. The specific activity with D-proline is 130% compared to the L-enantiomer. The bifunctional enzyme reversibly catalyzes the racemization of proline and the epimerization of 4-hydroxyproline and 3-hydroxyproline with similar kinetic constants. Catalysis is based on the same 1,1-proton transfer mechanism using two general acidic/basic cysteine residues located on opposite faces of the active site
-
-
r
L-proline
D-proline
-
the simplest mechanism for ProR isomerization of L-Pro to D-Pro entails the Cys130/Cys300 dyad in the thiolate/thiol forms, respectively, while His132 and Asp296 are in their neutral and carboxylate forms, in this scheme Cys130 is deprotonated either by a water molecule or an initially neutral form of the amine moiety of the substrate, thus, His132 and Asp296 do not serve a catalytic acid-base role in the racemization step but interact tightly with the ammonium moiety of the substrate, the ProR catalytic cycle involves 2 proton-transfer reactions in either direction of the racemization
-
-
r
additional information
?
-
TcPRACB: no reaction with L-hydroxyproline
-
?
additional information
?
-
TcPRACB: no reaction with L-hydroxyproline
-
?
additional information
?
-
-
TcPRACB: no reaction with L-hydroxyproline
-
?
additional information
?
-
-
a free and intact active site of the enzyme is necessary to allow mitogenicity
-
?
additional information
?
-
-
quantum mechanical and molecular mechanical study reveals two almost isoenergetic minima M1a and M2a, in which the enzyme is bound to L-proline and D-proline, respectively, and a transition state TSCa, unveiling a highly asynchronous concerted process. Residues Asn133, Asp296, and Gly301 destabilize M2a. Conversely, both Gly131 and Gly303 stabilize M2a. Residues Gly131, Gly301, and Thr302 stabilize TSCa
-
-
-
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
L-Pro
D-Pro
-
overexpression of TcPRAC leads to an increase in parasite differentiation into infective forms and its subsequent penetration into host cells. During infection of its mammalian host, the parasite secretes a proline racemase that contributes to parasite immune evasion by acting as a B-cell mitogen
-
-
?
additional information
?
-
-
a free and intact active site of the enzyme is necessary to allow mitogenicity
-
?
L-proline
D-proline
-
the simplest mechanism for ProR isomerization of L-Pro to D-Pro entails the Cys130/Cys300 dyad in the thiolate/thiol forms, respectively, while His132 and Asp296 are in their neutral and carboxylate forms, in this scheme Cys130 is deprotonated either by a water molecule or an initially neutral form of the amine moiety of the substrate, thus, His132 and Asp296 do not serve a catalytic acid-base role in the racemization step but interact tightly with the ammonium moiety of the substrate, the ProR catalytic cycle involves 2 proton-transfer reactions in either direction of the racemization
-
-
r
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
the enzyme is not pyridoxal 5'-phosphate-dependent
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(E)-4-oxopent-2-enoic acid
-
an irreversible strong competitive inhibitor, which hampers Trypanosoma cruzi intracellular differentiation and fate in mammalian host cells
(E)-5-bromo-4-oxopent-2-enoic acid
-
an irreversible strong competitive inhibitor, which hampers Trypanosoma cruzi intracellular differentiation and fate in mammalian host cells
7-azabicyclo[2.2.1]heptan-7-ium-1-carboxylate
-
a weak inhibitor of proline racemase, 29% inhibition at 142.5 mM
tetrahydro-1H-pyrrolizine-7a(5H)-carboxylate
-
a bicyclic substrate-product analogue and noncompetitive inhibitor of proline racemase
pyrrole-2-carboxylic acid
-
inhibitor significantly affects parasite infection of Vero cells in vitro, inhibitor also hampers Trypanosoma cruzi intracellular differentiation, inhibitor reduces host cell invasion in Vero cells by Trypanososma cruzi in a dose-dependent manner, pre-treatment of the parasites with 1 mM of inhibitor does not lead to changes in their morphology and motility, but results in an up to 54% reduction in the percentage of parasitized cells and about 30% less parasites per cell when cultures are counted at day 4 after infection
additional information
-
substrate-product analogue inhibitors of racemases may only be effective when the active site is capacious and/or plastic, or when the inhibitor is sufficiently flexible
-
additional information
-
synthesized soluble pyrazole derivatives prove to be weak or inactive TcPRAC inhibitors
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SH compounds
-
activate, e.g. 2-mercaptoethanol, 1,3-dimercaptoethanol
additional information
-
pyridoxal 5'-phosphate is not involved in racemization
-
additional information
-
addition of pyridoxal 5'-phosphate does not increase activity
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
106
D-proline
40 mM substrate in 0.2 M sodium acetate, for 30 min at 37°C
5.7
L-proline
-
pH and temperature not specified in the publication
145
L-proline
40 mM substrate in 0.2 M sodium acetate, for 30 min at 37°C
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.006 - 0.01
2-pyrrolecarboxylic acid
-
recombinant His-tagged enzyme, pH 6.0, 37°C
1
4-bromopyrazole-3-carboxylic acid
-
recombinant His-tagged enzyme, pH 6.0, 37°C
2
4-chloro-5-methyl-pyrazole-3-carboxylic acid
-
recombinant His-tagged enzyme, pH 6.0, 37°C
0.3
4-chloropyrazole-3-carboxylic acid
-
recombinant His-tagged enzyme, pH 6.0, 37°C
2
4-ethylpyrazole-3-carboxylic acid
-
recombinant His-tagged enzyme, pH 6.0, 37°C
111
tetrahydro-1H-pyrrolizine-7a(5H)-carboxylate
-
pH and temperature not specified in the publication
0.02
pyrrole-2-carboxylic acid
0.005 mM pyrrole-2-carboxylic acid, serial concentrations of 20-160 mM L-proline
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
349
1-carboxy-7-azoniabicyclo[2.2.1]heptane
Acetoanaerobium sticklandii
-
pH and temperature not specified in the publication
67
tetrahydro-1H-pyrrolizine-7a(5H)-carboxylate
Acetoanaerobium sticklandii
-
pH and temperature not specified in the publication
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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
6.6 - 8.1
-
pH 5.5: no detectable activity, rapid fall of activity below pH 6.5, activity is relatively stable between pH 6.7 and 8.1
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
50
90 - 100
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
TcPRAC localizes in the cytoplasm of intracellular amastigote forms of the parasite, near the flagellar pocket of the parasites
-
membrane-bound and secreted forms of enzyme are present upon differentiation of the parasite into non-dividing infective forms
-
membrane-bound and secreted forms of enzyme are present upon differentiation of the parasite into non-dividing infective forms
-
-
during infection of its mammalian host, the parasite secretes a proline racemase that contributes to parasite immune evasion by acting as a B-cell mitogen
-
-
in replicative non-infective forms of Trypanosoma cruzi
-
TcPRACB secretes the intracellular isoform of the enzyme. TcPRACA gene can generate both secreted and intracellular isoforms (by an alternative trans-splicing mechanism)
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PDB
SCOP
CATH
ORGANISM
UNIPROT
Brucella melitensis biotype 1 (strain 16M / ATCC 23456 / NCTC 10094)
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
40000
45000
80000
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SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homodimer
monomer
homodimer
-
enzyme comprises of 2 alpha/beta units containing 414 amino acids which are separated by a deep cleft. Each monomer possesses an independent active site pocket, which is sequestered from water
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Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
best crystals are obtained by mixing 2-3 microliter of the protein solution with an equal volume of crystallization buffer (0.1 M ammonium acetate/50 mM tri-sodium citrate dihydrate, pH 5.6/15% w/v polyethylene glycol 4000), equilibrated over 1 ml of the same buffer; crystal structure analysis shows that TcPRACA is a homodimer, with each monomer folded in two symmetric alpha/beta subunits separated by a deep crevice. The structure of TcPRACA in complex with a transition-state analog, pyrrole-2-carboxylic acid, reveals the presence of one reaction center per monomer, with two Cys residues optimally located to perform acid/base catalysis through a carbanion stabilization mechanism
-
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
80
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 50% glycerol or diluted in sodium acetate buffer, pH 6.0, activity is impaired
-
23°C, 0.5 M imidazole buffer, pH 8.0, 10 days, TcPRACA loses 84% of its activity
-
23°C, 0.5 M imidazole buffer, pH 8.0, 10 days, TcPRACB is stable, TcPRACA loses 84% of its activity
-
stored 6 months in the refrigerator without significant loss of activity
-
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
by affinity chromatography using nickel-nitrilotriacetic acid-agarose columns
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
-
recombinant His6-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
-
TcPRACA protein is purified with immobilized metal affinity chromatography on nickel columns. The active peak is further submitted to gel filtration chromatography at 2.5 ml/min in a Superdex200 26/60 column
-
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
expression in Escherichia coli BL21 (DE3) with a C-terminal 6-His tag
recombinant expression of His-tagged enzyme in Escherichia coli strain BL21(DE3)
-
recombinant expression of His6-tagged enzyme in Escherichia coli strain BL21(DE3)
-
the paralogous genes TcPRACA (A+) and TcPRACB (B++) are overexpressed in non-infective epimastigote forms using appropriate vectors to obtain stable chromosomal integration of these genes in sense and antisense orientations; the paralogous genes TcPRACA (A+) and TcPRACB (B++) are overexpressed in non-infective epimastigote forms using appropriate vectors to obtain stable chromosomal integration of these genes in sense and antisense orientations
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
2 paralogous copies of proline racemase genes are present per parasite haploid genome and they are differentially expressed during Trypanosoma cruzi development. Non-infective forms of the parasite expressing full length antisense TcPRACB RNA (functional knockdown) are not viable, whereas functional TcPRACA-knock down (A-) epimastigotes survive only poorly even under low selection pressure for recombinant parasites. Extracts from parasites overexpressing TcPRAC genes display more D-amino acid-containing peptides than wild type or knock down controls. The metacyclic form/epimastigote D-amino acid ratio obtained from parasites that developed in higher concentrations of proline (5.5) is greater than the metacyclic form/epimastigote D-amino acid ratio from wild type (2). Parasites overexpressing the intracytoplasmic isoform of proline racemase (B++) that has differentiated in 1x or 3x proline conditions display higher metacyclic form/epimastigote D-amino acid ratios than the respective wild type controls. Although they present a relative increase in metacyclic form/epimastigote D-amino acid ratios, overexpressors of the secreted version of TcPRAC (A+) show lower levels of D-amino acids than wild type or B++ parasites. Since TcPRACA transcripts appear to be more highly expressed at the end of metacyclogenesis, it is tempting to consider that racemisation of intracellular proline during this stage of development instead depends on the cytoplasmic version of the enzyme (TcPRACB); 2 paralogous copies of proline racemase genes are present per parasite haploid genome and they are differentially expressed during Trypanosoma cruzi development. Non-infective forms of the parasite expressing full length antisense TcPRACB RNA (functional knockdown) are not viable, whereas functional TcPRACA-knock down (A-) epimastigotes survive only poorly even under low selection pressure for recombinant parasites. Extracts from parasites overexpressing TcPRAC genes display more D-amino acid-containing peptides than wild type or knock down controls. The metacyclic form/epimastigote D-amino acid ratio obtained from parasites that developed in higher concentrations of proline (5.5) is greater than the metacyclic form/epimastigote D-amino acid ratio from wild type (2). Parasites overexpressing the intracytoplasmic isoform of proline racemase (B++) that has differentiated in 1x or 3x proline conditions display higher metacyclic form/epimastigote D-amino acid ratios than the respective wild type controls. Although they present a relative increase in metacyclic form/epimastigote D-amino acid ratios, overexpressors of the secreted version of TcPRAC (A+) show lower levels of D-amino acids than wild type or B++ parasites. Since TcPRACA transcripts appear to be more highly expressed at the end of metacyclogenesis, it is tempting to consider that racemisation of intracellular proline during this stage of development instead depends on the cytoplasmic version of the enzyme (TcPRACB)
in amastigote forms of the parasites, the intensity of anti-TcPRAC labeling varies according to the time post infection reaching the highest signal of TcPRAC expression after 48 h, while the number of intracellular parasites increases by amastigote multiplication
-
recombinant epimastigote parasites overexpressing TcPRAC genes coding for proline racemase present an augmented ability to differentiate into metacyclic infective forms and subsequently penetrate host-cells in vitro
-
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
R240W
mutant enzyme shows similar kinetic constants for proline and hydroxyproline as compared to the wild-type enzyme
W241F the mutant enzyme
C130S
-
mutation of the catalytic Cys residues abolishes the enzymatic activity but preserves the mitogenic properties of the protein
C300S
-
mutation of the catalytic Cys residues abolishes the enzymatic activity but preserves the mitogenic properties of the protein
W241F the mutant enzyme
H3ZMH5
shows 5.3fold, 430fold, and 5.8fold lower kcat/Km values for trans-4-hydroxy-L-proline, trans-3-hydroxy-L-proline, and cis-4-hydroxy-D-proline respectively, mainly due to a marked decrease in kcat values, whereas no significant effects are found in the kinetic constants of proline, suggesting that this (hydrophobic and bulky) tryptophan residue plays an importance role in the recognition of hydroxyproline (more hydrophilic and bulky than proline)
W241F the mutant enzyme
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shows 5.3fold, 430fold, and 5.8fold lower kcat/Km values for trans-4-hydroxy-L-proline, trans-3-hydroxy-L-proline, and cis-4-hydroxy-D-proline respectively, mainly due to a marked decrease in kcat values, whereas no significant effects are found in the kinetic constants of proline, suggesting that this (hydrophobic and bulky) tryptophan residue plays an importance role in the recognition of hydroxyproline (more hydrophilic and bulky than proline)
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
enzyme has potential to be used as a drug target for this parasite-based trypanosomiasis
medicine
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potential of the enzyme as a critical target for drug development against Chaga‘s disease. The enzyme is absent in mammalian host, suggesting that inhibition of proline racemase may have therapeutic potential; potential of the enzyme as a critical target for drug development against Chagas‘ disease. The enzyme is absent in mammalian host, suggesting that inhibition of proline racemase may have therapeutic potential
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LINKS TO OTHER DATABASES (specific for EC-Number 5.1.1.4)
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