Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
28  structures 2142  species 1  interaction 3283  sequences 17  architectures

Family: Pro_racemase (PF05544)

Summary: Proline racemase

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

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

Proline racemase Edit Wikipedia article

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

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

L-proline 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

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

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]


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–).


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


  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". Nature Medicine. 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". Molecular Microbiology. 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 1964878Freely accessible. 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". Molecular and Biochemical Parasitology. 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". Proceedings of the National Academy of Sciences. 103 (6): 1705–10. doi:10.1073/pnas.0509010103. PMC 1413642Freely accessible. PMID 16446443. 
  8. ^ Albery WJ, Knowles JR (May 1986). "Energetics and mechanism of proline racemase". Biochemistry. 25 (9): 2572–7. doi:10.1021/bi00357a043. PMID 3718964. 

Further reading

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 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

Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR008794

This family consists of proline racemase (EC), 4-hydroxyproline epimerase (EC), and trans-L-3-hydroxyproline dehydratase (EC).

Proline racemase catalyses the interconversion of L- and D-proline in bacteria [PUBMED:3755058]. Although the mechanisms of aminoacid racemisation and epimerisation are conserved between proline racemase and hydroxyproline epimerase, substrate specificity partly rely on constraints imposed by certain residues distinctively belonging to the catalytic pocket [PUBMED:17849014]. A human proline racemase-like gene, lacking a specific cysteine residue critical for racemase activity, has been identified as a trans-3-hydroxy-L-proline dehydratase [PUBMED:22528483]. This family also contains several proteins that remain uncharacterised.

Domain organisation

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

Loading domain graphics...

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


We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

Representative proteomes UniProt
Jalview View  View  View  View  View  View  View  View  View 
HTML View  View               
PP/heatmap 1 View               

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

Representative proteomes UniProt

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

Representative proteomes UniProt
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...


This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

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
Sequence Ontology: SO:0100021
Author: Moxon SJ
Number in seed: 14
Number in full: 3283
Average length of the domain: 312.20 aa
Average identity of full alignment: 35 %
Average coverage of the sequence by the domain: 95.07 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -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: 11
Download: download the raw HMM for this family

Species distribution

Sunburst controls


Weight segments by...

Change the size of the sunburst


Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls


The tree shows the occurrence of this domain across different species. More...


Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.


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



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 28 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 sequence.

Loading structure mapping...