Target type: molecularfunction
Catalysis of the reaction: peptidyl-proline (omega=180) = peptidyl-proline (omega=0). [EC:5.2.1.8]
Peptidyl-prolyl cis-trans isomerase (PPIase) activity is a crucial molecular function that plays a vital role in protein folding and function. PPIases catalyze the cis-trans isomerization of the peptide bond preceding proline residues. Proline, due to its cyclic structure, imposes constraints on protein folding by introducing a conformational rigidity. This makes the peptide bond preceding proline particularly slow to isomerize, often becoming a rate-limiting step in the folding process.
PPIases accelerate this isomerization reaction by lowering the activation energy barrier. They do this by binding to the peptide bond and facilitating the rotation around the peptide bond, thereby allowing the proline residue to switch between its cis and trans conformations. This isomerization is essential for achieving the correct three-dimensional structure of proteins.
The cis and trans conformations of the peptide bond preceding proline have significant impact on protein folding. The cis conformation often leads to a tight turn or loop structure, while the trans conformation allows for a more extended polypeptide chain. The correct isomerization state at each proline residue is crucial for proper protein folding, stability, and function.
PPIases are essential for various cellular processes, including:
* **Protein Folding:** They assist in the proper folding of newly synthesized proteins by facilitating the isomerization of proline residues.
* **Protein Maturation:** PPIases can contribute to the correct folding and assembly of multi-subunit protein complexes.
* **Signal Transduction:** Some PPIases are involved in regulating signaling pathways by modulating the activity of signaling proteins.
* **Cellular Stress Response:** PPIases can help in the refolding of misfolded or unfolded proteins under stress conditions, preventing protein aggregation.
PPIase activity is found in a wide range of organisms and is associated with different classes of enzymes, including cyclophilins, FK506-binding proteins, and parvulins. Each class exhibits distinct structural features and mechanisms, but they all share the ability to catalyze the isomerization of the peptide bond preceding proline residues.'
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Protein | Definition | Taxonomy |
---|---|---|
Peptidyl-prolyl cis-trans isomerase FKBP1A | [no definition available] | Bos taurus (cattle) |
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 | A peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q13526] | Homo sapiens (human) |
Serine/threonine-protein phosphatase 2A activator | A serine/threonine-protein phosphatase 2A regulatory subunit B that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q15257] | Homo sapiens (human) |
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 4 | A peptidyl-prolyl cis-trans isomerase NIMA-interacting 4 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y237] | Homo sapiens (human) |
Peptidyl-prolyl cis-trans isomerase FKBP14 | A peptidyl-prolyl cis-trans isomerase FKBP14 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9NWM8] | Homo sapiens (human) |
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 | A peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q13526] | Homo sapiens (human) |
Peptidyl-prolyl cis-trans isomerase FKBP5 | A peptidyl-prolyl cis-trans isomerase FKBP5 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q13451] | Homo sapiens (human) |
Peptidyl-prolyl cis-trans isomerase D | A eukaryotic-type peptidyl-prolyl cis-trans isomerase D that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q08752] | Homo sapiens (human) |
Peptidyl-prolyl cis-trans isomerase FKBP4 | A peptidyl-prolyl cis-trans isomerase FKBP4 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q02790] | Homo sapiens (human) |
Peptidyl-prolyl cis-trans isomerase FKBP3 | A peptidyl-prolyl cis-trans isomerase FKBP3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q00688] | Homo sapiens (human) |
Peptidyl-prolyl cis-trans isomerase FKBP1B | A peptidyl-prolyl cis-trans isomerase FKBP1B that is encoded in the genome of human. [PRO:DNx, UniProtKB:P68106] | Homo sapiens (human) |
Peptidyl-prolyl cis-trans isomerase FKBP1A | A peptidyl-prolyl cis-trans isomerase FKBP1A that is encoded in the genome of human. [PRO:DNx, UniProtKB:P62942] | Homo sapiens (human) |
Peptidyl-prolyl cis-trans isomerase A | A peptidyl-prolyl cis-trans isomerase A that is encoded in the genome of human. [PRO:DNx, UniProtKB:P62937] | Homo sapiens (human) |
Peptidyl-prolyl cis-trans isomerase F, mitochondrial | A peptidyl-prolyl cis-trans isomerase F, mitochondrial that is encoded in the genome of human. [PRO:DNx, UniProtKB:P30405] | Homo sapiens (human) |
Peptidyl-prolyl cis-trans isomerase B | A eukaryotic peptidyl-prolyl cis-trans isomerase B that is encoded in the genome of human. [PRO:DNx, UniProtKB:P23284] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
imidazole | 1H-imidazole : An imidazole tautomer which has the migrating hydrogen at position 1. imidazole: RN given refers to parent cpd | imidazole | |
juglone | juglone : A hydroxy-1,4-naphthoquinone that is 1,4-naphthoquinone in which the hydrogen at position 5 has been replaced by a hydroxy group. A plant-derived 1,4-naphthoquinone with confirmed antibacterial and antitumor activities. juglone: structure | hydroxy-1,4-naphthoquinone | geroprotector; herbicide; reactive oxygen species generator |
thiabendazole | Tresaderm: dermatologic soln containing dexamethasone, thiabendazole & neomycin sulfate | 1,3-thiazoles; benzimidazole fungicide; benzimidazoles | antifungal agrochemical; antinematodal drug |
cycloheximide | cycloheximide : A dicarboximide that is 4-(2-hydroxyethyl)piperidine-2,6-dione in which one of the hydrogens attached to the carbon bearing the hydroxy group is replaced by a 3,5-dimethyl-2-oxocyclohexyl group. It is an antibiotic produced by the bacterium Streptomyces griseus. Cycloheximide: Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis. | antibiotic fungicide; cyclic ketone; dicarboximide; piperidine antibiotic; piperidones; secondary alcohol | anticoronaviral agent; bacterial metabolite; ferroptosis inhibitor; neuroprotective agent; protein synthesis inhibitor |
1,4-naphthoquinone | 1,4-naphthoquinone : The parent structure of the family of 1,4-naphthoquinones, in which the oxo groups of the quinone moiety are at positions 1 and 4 of the naphthalene ring. Derivatives have pharmacological properties. naphthoquinone : A polycyclic aromatic ketone metabolite of naphthalene. | 1,4-naphthoquinones | |
2-hydroxypyridine | hydroxypyridine : Any member of the class of pyridines with at least one hydroxy substituent. pyridin-2-ol : A monohydroxypyridine that is pyridine substituted by a hydroxy group at position 2. | monohydroxypyridine | plant metabolite |
glycyrrhetinic acid | cyclic terpene ketone; hydroxy monocarboxylic acid; pentacyclic triterpenoid | immunomodulator; plant metabolite | |
2,4-pyridinedicarboxylic acid | lutidinic acid : A pyridinedicarboxylic acid carrying carboxy groups at positions 2 and 4. | pyridinedicarboxylic acid | |
2-piperidone | 2-piperidone: structure given in first source piperidin-2-one : A delta-lactam that is piperidine which is substituted by an oxo group at position 2. | delta-lactam; piperidones | EC 1.2.1.88 (L-glutamate gamma-semialdehyde dehydrogenase) inhibitor |
4-methylimidazole | 4-methylimidazole : Imidazole substituted at position 4 by a methyl group. 4-methylimidazole: RN given refers to parent cpd | imidazoles | carcinogenic agent; reaction intermediate |
daminozide | daminozide: induces tumors | straight-chain fatty acid | |
epigallocatechin gallate | (-)-epigallocatechin 3-gallate : A gallate ester obtained by the formal condensation of gallic acid with the (3R)-hydroxy group of (-)-epigallocatechin. epigallocatechin gallate: a steroid 5alpha-reductase inhibitor and antimutagen in green tea (Camellia sinensis) | flavans; gallate ester; polyphenol | antineoplastic agent; antioxidant; apoptosis inducer; geroprotector; Hsp90 inhibitor; neuroprotective agent; plant metabolite |
propazole | propazole: RN given refers to parent cpd; structure | benzimidazoles | |
prolinal | pyrrolidines | ||
Tautomycin | carboxylic ester | ||
tretinoin | all-trans-retinoic acid : A retinoic acid in which all four exocyclic double bonds have E- (trans-) geometry. retinoic acid : A retinoid consisting of 3,7-dimethylnona-2,4,6,8-tetraenoic acid substituted at position 9 by a 2,6,6-trimethylcyclohex-1-en-1-yl group (geometry of the four exocyclic double bonds is not specified). Tretinoin: An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE). | retinoic acid; vitamin A | anti-inflammatory agent; antineoplastic agent; antioxidant; AP-1 antagonist; human metabolite; keratolytic drug; retinoic acid receptor agonist; retinoid X receptor agonist; signalling molecule |
3-(3-pyridyl)-1-propyl-(2s)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-pyrrolidinecarboxylate | |||
tacrolimus | tacrolimus (anhydrous) : A macrolide lactam containing a 23-membered lactone ring, originally isolated from the fermentation broth of a Japanese soil sample that contained the bacteria Streptomyces tsukubaensis. Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. | macrolide lactam | bacterial metabolite; immunosuppressive agent |
N-(2-fluorophenyl)-2-[2-(4-thiazolyl)-1-benzimidazolyl]acetamide | benzimidazoles | ||
biricodar | biricodar: a non-macrocyclic ligand for FKBP12; structure in first source | alpha-amino acid ester | |
oxalylglycine | N-oxalylglycine : An amino dicarboxylic acid that is iminodiacetic acid with an oxo substituent. It is used as an inhibitor of alpha-ketoglutarate dependent (EC 1.14.11.*) enzymes. oxalylglycine: structure given in first source | amino dicarboxylic acid; N-acylglycine | EC 1.14.11.* (oxidoreductase acting on paired donors, 2-oxoglutarate as one donor, incorporating 1 atom each of oxygen into both donors) inhibitor |
pd 407824 | |||
l 683590 | immunomycin: from Streptomyces hygroscopicus; structure given in first source | ether; lactol; macrolide; secondary alcohol | antifungal agent; bacterial metabolite; immunosuppressive agent |
cyclosporine | ramihyphin A: one of the metabolites produced by Fusarium sp. S-435; RN given refers to cpd with unknown MF | homodetic cyclic peptide | anti-asthmatic drug; anticoronaviral agent; antifungal agent; antirheumatic drug; carcinogenic agent; dermatologic drug; EC 3.1.3.16 (phosphoprotein phosphatase) inhibitor; geroprotector; immunosuppressive agent; metabolite |
sirolimus | sirolimus : A macrolide lactam isolated from Streptomyces hygroscopicus consisting of a 29-membered ring containing 4 trans double bonds, three of which are conjugated. It is an antibiotic, immunosupressive and antineoplastic agent. Sirolimus: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties. | antibiotic antifungal drug; cyclic acetal; cyclic ketone; ether; macrolide lactam; organic heterotricyclic compound; secondary alcohol | antibacterial drug; anticoronaviral agent; antineoplastic agent; bacterial metabolite; geroprotector; immunosuppressive agent; mTOR inhibitor |
sanglifehrin a | sanglifehrin A: binds cyclophilin A; isolated from Streptomyces; structure in first source | ||
(melle-4)cyclosporin | (melle-4)cyclosporin: a non-immunosuppressive analog of cyclosporin A | ||
cyclosporin g | cyclosporin G: similar immunosuppressive actions as cyclosporin, but without nephrotoxic side effects; cyclosporin A analog; MW 1217 | ||
scy-635 | |||
bastadin 5 | |||
timcodar | timcodar: a mutlidrug resistance inhibitor; structure in first source | ||
acetyl-11-ketoboswellic acid | acetyl-11-ketoboswellic acid: a 5-lipoxygenase inhibitor; structure given in first source | triterpenoid | |
nutlin-3a | nutlin 3: an MDM2 antagonist; structure in first source | stilbenoid | |
alisporivir | alisporivir: nonimmunosuppressive cyclosporin analog; structure/sequence in first source | homodetic cyclic peptide | anticoronaviral agent |