This enzyme belongs to the family of proline racemases acting on free amino acids. The systematic name of this enzyme class is proline racemase. This enzyme participates in arginine and proline metabolism. These enzymes catalyse the interconversion of L- and D-proline in bacteria.[1]
Species distribution
This first eukaryotic proline racemase was identified in Trypanosoma cruzi and fully characterized Q9NCP4. The parasite enzyme, TcPRAC, is as a co-factor-independent proline racemase and displays B-cell mitogenic properties when released by T. cruzi upon infection, contributing to parasite escape.[2][3]
Novel proline racemases of medical and veterinary importance were described respectively in Clostridioides difficile (bacteria) (Q17ZY4)[4] and Trypanosoma vivax (B8LFE4).[5] These studies showed that a peptide motif used as a minimal pattern signature to identify putative proline racemases (motif III*) is insufficient stringent per se to discriminate proline racemases from 4-hydroxyproline epimerases (HyPRE). Also, additional, non-dissociated elements that account for the discrimination of these enzymes were identified, based for instance on polarity constraints imposed by specific residues of the catalytic pockets. Based on those elements, enzymes incorrectly described as proline racemases were biochemically proved to be hydroxyproline epimerases (i.e. HyPREs from Pseudomonas aeruginosa (Q9I476), Burkholderia pseudomallei (Q63NG7), Brucella abortus (Q57B94), Brucella suis (Q8FYS0) and Brucella melitensis (Q8YJ29).[4]
Structural studies
The biochemical mechanism of proline racemase was first put forward in the late sixties by Cardinale and Abeles[6] using the Clostridium sticklandii enzyme, CsPRAC. The catalytic mechanism of proline racemase was late revisited by Buschiazzo, Goytia and collaborators that, in 2006, resolved the structure of the parasite TcPRAC co-crystallyzed with its known competitive inhibitor - pyrrole carboxylic acid (PYC).[7] Those studies showed that each active enzyme contains two catalytic pockets. Isothermal titration calorimetry then showed that two molecules of PYC associate with TcPRAC in solution, and that this association is time-dependent and most probably based on mechanism of negative cooperativity. Complementary biochemical findings are consistent with the presence of two active catalytic sites per homodimer, each pertaining to one enzyme subunit, challenging the previously proposed mechanism of one catalytic site per homodimer previously proposed.[8]
Mechanism
The proline racemase active site contains two general bases, each of them a Cys, located on either side of the alpha-carbon of the substrate. In order to work properly, one Cys must be protonated (a thiol, RSH) and the other must be deprotonated (a thiolate, RS–).
Inhibition
Proline racemase is inhibited by pyrrole-2-carboxylic acid, a transition state analogue that is flat like the transition state.
Related Research Articles
In chemistry, hydroxylation can refer to:
In biochemistry, isomerases are a general class of enzymes that convert a molecule from one isomer to another. Isomerases facilitate intramolecular rearrangements in which bonds are broken and formed. The general form of such a reaction is as follows:
Trypanosoma is a genus of kinetoplastids, a monophyletic group of unicellular parasitic flagellate protozoa. Trypanosoma is part of the phylum Euglenozoa. The name is derived from the Greek trypano- (borer) and soma (body) because of their corkscrew-like motion. Most trypanosomes are heteroxenous and most are transmitted via a vector. The majority of species are transmitted by blood-feeding invertebrates, but there are different mechanisms among the varying species. Trypanosoma equiperdum is spread between horses and other equine species by sexual contact. They are generally found in the intestine of their invertebrate host, but normally occupy the bloodstream or an intracellular environment in the vertebrate host.
Phosphopentose epimerase encoded in humans by the RPE gene is a metalloprotein that catalyzes the interconversion between D-ribulose 5-phosphate and D-xylulose 5-phosphate.
Procollagen-proline dioxygenase, commonly known as prolyl hydroxylase, is a member of the class of enzymes known as alpha-ketoglutarate-dependent hydroxylases. These enzymes catalyze the incorporation of oxygen into organic substrates through a mechanism that requires alpha-Ketoglutaric acid, Fe2+, and ascorbate. This particular enzyme catalyzes the formation of (2S, 4R)-4-hydroxyproline, a compound that represents the most prevalent post-translational modification in the human proteome.
In enzymology, a trypanothione-disulfide reductase (EC 1.8.1.12) is an enzyme that catalyzes the chemical reaction
In enzymology, a 2-aminohexano-6-lactam racemase is an enzyme that catalyzes the chemical reaction
In enzymology, an alanine racemase is an enzyme that catalyzes the chemical reaction
α-Methylacyl-CoA racemase is an enzyme that in humans is encoded by the AMACR gene. AMACR catalyzes the following chemical reaction:
In enzymology, an aspartate racemase is an enzyme that catalyzes the following chemical reaction:
In enzymology, a diaminopimelate epimerase is an enzyme that catalyzes the chemical reaction
In enzymology, glutamate racemase is an enzyme that catalyzes the chemical reaction
In enzymology, a L-ribulose-5-phosphate 4-epimerase is an enzyme that catalyzes the interconversion of ribulose 5-phosphate and xylulose 5-phosphate in the oxidative phase of the Pentose phosphate pathway.
The enzyme lactoylglutathione lyase (EC 4.4.1.5, also known as glyoxalase I) catalyzes the isomerization of hemithioacetal adducts, which are formed in a spontaneous reaction between a glutathionyl group and aldehydes such as methylglyoxal.
In enzymology, a trypanothione synthase (EC 6.3.1.9) is an enzyme that catalyzes the chemical reaction
Cruzipain is a cysteine protease expressed by Trypanosoma cruzi.
Dihydroorotate dehydrogenase (fumarate) (EC 1.3.98.1, dihydroorotate oxidase, pyr4 (gene)) is an enzyme with systematic name (S)-dihydroorotate:fumarate oxidoreductase. This enzyme catalyses the following chemical reaction
Trypanosoma vivax is a parasite species in the genus Trypanosoma. It causes the disease nagana, affecting cattle or wild mammals. It is mainly occurs in West Africa, although it has spread to South America.
Oxidosqualene cyclases (OSC) are enzymes involved in cyclization reactions of 2,3-oxidosqualene to form sterols or triterpenes.
Papain-like proteases are a large protein family of cysteine protease enzymes that share structural and enzymatic properties with the group's namesake member, papain. They are found in all domains of life. In animals, the group is often known as cysteine cathepsins or, in older literature, lysosomal peptidases. In the MEROPS protease enzyme classification system, papain-like proteases form Clan CA. Papain-like proteases share a common catalytic dyad active site featuring a cysteine amino acid residue that acts as a nucleophile.
References
↑ Fisher LM, Albery WJ, Knowles JR (May 1986). "Energetics of proline racemase: racemization of unlabeled proline in the unsaturated, saturated, and oversaturated regimes". Biochemistry. 25 (9): 2529–37. doi:10.1021/bi00357a037. PMID3755058.
↑ Reina-San-Martín B, Degrave W, Rougeot C, Cosson A, Chamond N, Cordeiro-Da-Silva A, Arala-Chaves M, Coutinho A, Minoprio P (August 2000). "A B-cell mitogen from a pathogenic trypanosome is a eukaryotic proline racemase". Nature Medicine. 6 (8): 890–7. doi:10.1038/78651. PMID10932226. S2CID9163196.
↑ Chamond N, Cosson A, Coatnoan N, Minoprio P (June 2009). "Proline racemases are conserved mitogens: characterization of a Trypanosoma vivax proline racemase". Molecular and Biochemical Parasitology. 165 (2): 170–9. doi:10.1016/j.molbiopara.2009.02.002. PMID19428664.
↑ Cardinale GJ, Abeles RH (November 1968). "Purification and mechanism of action of proline racemase". Biochemistry. 7 (11): 3970–8. doi:10.1021/bi00851a026. PMID5722267.
Stenta M, Calvaresi M, Altoè P, Spinelli D, Garavelli M, Bottoni A (January 2008). "The catalytic activity of proline racemase: a quantum mechanical/molecular mechanical study". The Journal of Physical Chemistry B. 112 (4): 1057–9. doi:10.1021/jp7104105. PMID18044876.
This page is based on this Wikipedia article Text is available under the CC BY-SA 4.0 license; additional terms may apply. Images, videos and audio are available under their respective licenses.
