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7  structures 740  species 1  interaction 1248  sequences 8  architectures

Family: Pro_racemase (PF05544)

Summary: Proline racemase

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This is the Wikipedia entry entitled "Proline racemase". More...

Proline racemase Edit Wikipedia article

proline racemase
Identifiers
EC number 5.1.1.4
CAS number 9024-09-3
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
Proline racemase
Identifiers
Symbol Pro_racemase
Pfam PF05544
InterPro IPR008794

In enzymology, a proline racemase (EC 5.1.1.4) is an enzyme that catalyzes the chemical reaction

L-proline \rightleftharpoons D-proline

Hence, this enzyme has two substrates, L- and D-proline, and two products, D- and L- proline.

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[edit]

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 Clostridium difficile (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[edit]

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[edit]

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[edit]

Proline racemase is inhibited by pyrrole-2-carboxylic acid, a transition state analogue that is flat like the transition state.

References[edit]

  1. ^ 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. PMID 3755058. 
  2. ^ 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". Nat. Med. 6 (8): 890–7. doi:10.1038/78651. PMID 10932226. 
  3. ^ Chamond N, Goytia M, Coatnoan N, Barale JC, Cosson A, Degrave WM, Minoprio P (October 2005). "Trypanosoma cruzi proline racemases are involved in parasite differentiation and infectivity". Mol. Microbiol. 58 (1): 46–60. doi:10.1111/j.1365-2958.2005.04808.x. PMID 16164548. 
  4. ^ a b Goytia M, Chamond N, Cosson A, Coatnoan N, Hermant D, Berneman A, Minoprio P (2007). "Molecular and structural discrimination of proline racemase and hydroxyproline-2-epimerase from nosocomial and bacterial pathogens". PLoS ONE 2 (9): e885. doi:10.1371/journal.pone.0000885. PMC 1964878. PMID 17849014. 
  5. ^ Chamond N, Cosson A, Coatnoan N, Minoprio P (June 2009). "Proline racemases are conserved mitogens: characterization of a Trypanosoma vivax proline racemase". Mol. Biochem. Parasitol. 165 (2): 170–9. doi:10.1016/j.molbiopara.2009.02.002. PMID 19428664. 
  6. ^ Cardinale GJ, Abeles RH (November 1968). "Purification and mechanism of action of proline racemase". Biochemistry 7 (11): 3970–8. doi:10.1021/bi00851a026. PMID 5722267. 
  7. ^ PDB 1W61 and PDB 1W62; Buschiazzo A, Goytia M, Schaeffer F, Degrave W, Shepard W, Grégoire C, Chamond N, Cosson A, Berneman A, Coatnoan N, Alzari PM, Minoprio P (February 2006). "Crystal structure, catalytic mechanism, and mitogenic properties of Trypanosoma cruzi proline racemase". Proc. Natl. Acad. Sci. U.S.A. 103 (6): 1705–10. doi:10.1073/pnas.0509010103. PMC 1413642. PMID 16446443. 
  8. ^ Albery WJ, Knowled JR (May 1986). "Energetics and mechanism of proline racemase". Biochemistry 25 (9): 2572–7. doi:10.1021/bi00357a043. PMID 3718964. 

Further reading[edit]

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Proline racemase Provide feedback

This family consists of proline racemase (EC 5.1.1.4) proteins which catalyse the interconversion of L- and D-proline in bacteria [1]. This family also contains several similar eukaryotic proteins including Q9NCP4 a sequence with B-cell mitogenic properties which has been characterised as a co-factor-independent proline racemase [2].

Literature references

  1. Fisher LM, Albery WJ, Knowles JR; , Biochemistry 1986;25:2529-2537.: Energetics of proline racemase: racemization of unlabeled proline in the unsaturated, saturated, and oversaturated regimes. PUBMED:3755058 EPMC:3755058

  2. Reina-San-Martin B, Degrave W, Rougeot C, Cosson A, Chamond N, Cordeiro-Da-Silva A, Arala-Chaves M, Coutinho A, Minoprio P; , Nat Med 2000;6:890-897.: A B-cell mitogen from a pathogenic trypanosome is a eukaryotic proline racemase. PUBMED:10932226 EPMC:10932226


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR008794

This family consists of proline racemase (EC) proteins which catalyse the interconversion of L- and D-proline in bacteria [PUBMED:3755058]. This family also contains several similar eukaryotic proteins including SWISSPROT a sequence with B-cell mitogenic properties which has been characterised as a co-factor-independent proline racemase [PUBMED:10932226].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan DAP_epimerase (CL0288), which has the following description:

This superfamily includes DAP epimerase and proline racemase as well as the PrpF protein. It has been suggested that this fold may have evolved from the HotDog fold [1].

The clan contains the following 4 members:

DAP_epimerase PhzC-PhzF Pro_racemase PrpF

Alignments

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(14)
Full
(1248)
Representative proteomes NCBI
(1522)
Meta
(561)
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(106)
RP35
(211)
RP55
(297)
RP75
(380)
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  Seed
(14)
Full
(1248)
Representative proteomes NCBI
(1522)
Meta
(561)
RP15
(106)
RP35
(211)
RP55
(297)
RP75
(380)
Alignment:
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  Seed
(14)
Full
(1248)
Representative proteomes NCBI
(1522)
Meta
(561)
RP15
(106)
RP35
(211)
RP55
(297)
RP75
(380)
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_7562 (release 8.0)
Previous IDs: none
Type: Family
Author: Moxon SJ
Number in seed: 14
Number in full: 1248
Average length of the domain: 313.20 aa
Average identity of full alignment: 35 %
Average coverage of the sequence by the domain: 95.24 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 19.5 19.5
Trusted cut-off 19.5 19.5
Noise cut-off 19.4 19.4
Model length: 325
Family (HMM) version: 6
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Species distribution

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Interactions

There is 1 interaction for this family. More...

Pro_racemase

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Pro_racemase domain has been found. There are 7 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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