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L-azetidine-2-carboxylate
D-azetidine-2-carboxylate
L-pipecolate
D-pipecolate
additional information
?
-
D-proline

L-proline
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
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
low activity
-
-
?
L-azetidine-2-carboxylate
D-azetidine-2-carboxylate
low activity
-
-
?
L-pipecolate

D-pipecolate
low activity
-
-
?
L-pipecolate
D-pipecolate
low activity
-
-
?
L-Pro

D-Pro
-
-
-
-
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
-
-
-
-
r
L-proline
D-proline
-
-
-
r
L-proline
D-proline
-
two-base racemization mechanism via an aci-carboxylate intermediate
-
-
r
L-proline
D-proline
-
-
-
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
M0LMI3;
the enzyme can utilize both proline and hydroxyprolines as substrate
-
-
r
L-proline
D-proline
M0LMI3;
the enzyme can utilize both proline and hydroxyprolines as substrate
-
-
r
L-proline
D-proline
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 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
-
-
-
-
?
L-proline
D-proline
-
-
-
-
r
L-proline
D-proline
-
-
?
L-proline
D-proline
-
-
-
-
L-proline
D-proline
-
-
-
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
L-proline
D-proline
-
-
-
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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Stadtman, T.C.; Elliott, P.
Studies on the enzymic reduction of amino acids. II. Purification and properties of a D-proline reductase and a proline racemase from Clostridium sticklandii
J. Biol. Chem.
228
983-997
1957
Acetoanaerobium sticklandii
brenda
Cardinale, G.J.; Abeles, R.H.
Purification and mechanism of action of proline racemase
Biochemistry
7
3970-3978
1968
Acetoanaerobium sticklandii
brenda
Keenan, M.V.; Alworth, W.L.
The inhibition of proline racemase by a transition state analogue: DELTA-1-pyrroline-2-carboxylate
Biochem. Biophys. Res. Commun.
57
500-504
1974
Acetoanaerobium sticklandii
brenda
Rudnick, G.; Abeles, R.H.
Reaction mechanism and structure of the active site of proline racemase
Biochemistry
14
4515-4522
1975
Acetoanaerobium sticklandii
brenda
Fisher, L.M.; Albery, W.J.; Knowles, J.R.
Energetics of proline racemase: racemization of unlabeled proline in the unsaturated, saturated and oversaturated regimes
Biochemistry
25
2529-2537
1986
Acetoanaerobium sticklandii
brenda
Fisher, L.M.; Belasco, J.G.; Bruice, T.W.; Albery, W.J.; Knowles, J.R.
Energetics of proline racemase: transition-state fractionation factors for the two protons involved in the catalytic steps
Biochemistry
25
2543-2551
1986
Acetoanaerobium sticklandii
brenda
Belasco, J.G.; Bruice, T.W.; Fisher, L.M.; Albery, W.J.; Knowles, J.R.
Energetics of proline racemase: rates, fractionation factors, and buffer catalysis in the oversaturated region. Nature of the interconversion of the two forms of free enzyme
Biochemistry
25
2564-2571
1986
Acetoanaerobium sticklandii
brenda
Fisher, L.M.; Albery, W.J.; Knowles, J.R.
Energetics of proline racemase: tracer perturbation experiments using [14C]proline that measure the interconversion rate of the two forms of free enzyme
Biochemistry
25
2538-2542
1986
Acetoanaerobium sticklandii
brenda
Belasco, J.G.; Bruice, T.W.; Albery, W.J.; Knowles, J.R.
Energetics of proline racemase: fractionation factors for the essential catalytic groups in the enzyme-substrate complexes
Biochemistry
25
2558-2564
1986
Acetoanaerobium sticklandii
brenda
Albery, W.J.; Knowles, J.R.
Energetics and mechanism of proline racemase
Biochemistry
25
2572-2577
1986
Acetoanaerobium sticklandii
brenda
Belasco, J.G.; Albery, W.J.; Knowles, J.R.
Energetics of proline racemase: double fractionation experiment, a test for concertedness and for transition-state dominance
Biochemistry
25
2552-2558
1986
Acetoanaerobium sticklandii
brenda
Chamond, N.; Gregoire, C.; Coatnoan, N.; Rougeot, C.; Freitas-Junior, L.H.; da Silveira, J.F.; Degrave, W.M.; Minoprio, P.
Biochemical characterization of proline racemases from the human protozoan parasite Trypanosoma cruzi and definition of putative protein signatures
J. Biol. Chem.
278
15484-15494
2003
Trypanosoma cruzi (Q4DA80), Trypanosoma cruzi (Q868H8), Trypanosoma cruzi
brenda
Reina-San-Martin, B.; Degrave, W.; Rougeot, C.; Cosson, A.; Chamond, N.; Cordeiro-Da-Silva, A.; Arala-Chaves, M.; Coutinho, A.; Minoprio, P.
A B-cell mitogen from a pathogenic trypanosome is a eukaryotic proline racemase
Nat. Med.
6
890-897
2000
Trypanosoma cruzi (Q4DA80), Trypanosoma cruzi
brenda
Chamond, N.; Goytia, M.; Coatnoan, N.; Barale, J.C.; Cosson, A.; Degrave, W.M.; Minoprio, P.
Trypanosoma cruzi proline racemases are involved in parasite differentiation and infectivity
Mol. Microbiol.
58
46-60
2005
Trypanosoma cruzi (Q4DA80), Trypanosoma cruzi
brenda
Stenta, M.; Calvaresi, M.; Altoe, P.; Spinelli, D.; Garavelli, M.; Bottoni, A.
The Catalytic Activity of Proline Racemase: A Quantum Mechanical/Molecular Mechanical Study
J. Phys. Chem. B
112
1057-1059
2008
Trypanosoma cruzi (Q4DA80), Trypanosoma cruzi
brenda
Goytia, M.; Chamond, N.; Cosson, A.; Coatnoan, N.; Hermant, D.; Berneman, A.; Minoprio, P.
Molecular and structural discrimination of proline racemase and hydroxyproline-2-epimerase from nosocomial and bacterial pathogens
PLoS ONE
2
e885
2007
Clostridioides difficile (A8DEZ8), Clostridioides difficile VPI10463 (A8DEZ8)
brenda
Buschiazzo, A.; Goytia, M.; Schaeffer, F.; Degrave, W.; Shepard, W.; Gregoire, C.; Chamond, N.; Cosson, A.; Berneman, A.; Coatnoan, N.; Alzari, P.M.; Minoprio, P.
Crystal structure, catalytic mechanism, and mitogenic properties of Trypanosoma cruzi proline racemase
Proc. Natl. Acad. Sci. USA
103
1705-1710
2006
Trypanosoma cruzi (Q4DA80), Trypanosoma cruzi
brenda
Rubinstein, A.; Major, D.T.
Catalyzing racemizations in the absence of a cofactor: the reaction mechanism in proline racemase
J. Am. Chem. Soc.
131
8513-8521
2009
Trypanosoma cruzi
brenda
Fonknechten, N.; Perret, A.; Perchat, N.; Tricot, S.; Lechaplais, C.; Vallenet, D.; Vergne, C.; Zaparucha, A.; Le Paslier, D.; Weissenbach, J.; Salanoubat, M.
A conserved gene cluster rules anaerobic oxidative degradation of L-ornithine
J. Bacteriol.
191
3162-3167
2009
Acetoanaerobium sticklandii (Q9L4Q3)
brenda
Coutinho, L.; Ferreira, M.A.; Cosson, A.; Batista, M.M.; Batista, D.d.a..G.; Minoprio, P.; Degrave, W.M.; Berneman, A.; Soeiro Mde, N.
Inhibition of Trypanosoma cruzi proline racemase affects host-parasite interactions and the outcome of in vitro infection
Mem. Inst. Oswaldo Cruz
104
1055-1062
2009
Trypanosoma cruzi
brenda
Coatnoan, N.; Berneman, A.; Chamond, N.; Minoprio, P.
Proline racemases: Insights into Trypanosoma cruzi peptides containing D-proline
Mem. Inst. Oswaldo Cruz
104
295-300
2009
Trypanosoma cruzi (Q4D480), Trypanosoma cruzi (Q868H8), Trypanosoma cruzi
brenda
Chamond, N.; Cosson, A.; Coatnoan, N.; Minoprio, P.
Proline racemases are conserved mitogens: characterization of a Trypanosoma vivax proline racemase
Mol. Biochem. Parasitol.
165
170-179
2009
Trypanosoma vivax (B8LFE4), Trypanosoma vivax
brenda
Bryan, M.; Norris, K.
Genetic immunization converts the Trypanosoma cruzi B-cell mitogen proline racemase to an effective immunogen
Infect. Immun.
78
810-822
2010
Trypanosoma cruzi, Trypanosoma cruzi Y
brenda
Harty, M.; Nagar, M.; Atkinson, L.; Legay, C.M.; Derksen, D.J.; Bearne, S.L.
Inhibition of serine and proline racemases by substrate-product analogues
Bioorg. Med. Chem. Lett.
24
390-393
2014
Acetoanaerobium sticklandii
brenda
Wu, X.; Hurdle, J.G.
The Clostridium difficile proline racemase is not essential for early logarithmic growth and infection
Can. J. Microbiol.
60
251-254
2014
Clostridioides difficile
brenda
Berneman, A.; Montout, L.; Goyard, S.; Chamond, N.; Cosson, A.; dArchivio, S.; Gouault, N.; Uriac, P.; Blondel, A.; Minoprio, P.
Combined approaches for drug design points the way to novel proline racemase inhibitor candidates to fight Chagas disease
PLoS ONE
8
e60955
2013
Trypanosoma cruzi
brenda
Watanabe, S.; Tanimoto, Y.; Nishiwaki, H.; Watanabe, Y.
Identification and characterization of bifunctional proline racemase/hydroxyproline epimerase from archaea: discrimination of substrates and molecular evolution
PLoS One
10
e0120349
2015
Clostridioides difficile (Q17ZY4), Ferroplasma acidarmanus (S0APF4), Haloarcula japonica (M0LMI3), Haloarcula japonica DSM 6131 (M0LMI3), Thermococcus litoralis (H3ZMH5), Thermococcus litoralis, Thermococcus litoralis DSM 5473 (H3ZMH5)
brenda