Parvulin, a 92-amino acid

Amino acid

Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

 protein discovered in E. coli in 1994, is the smallest known protein with prolyl isomerase

Prolyl isomerase

Prolyl isomerase is an enzyme found in both prokaryotes and eukaryotes that interconverts the cis and trans isomers of peptide bonds with the amino acid proline. Proline has an unusually conformationally restrained peptide bond due to its cyclic structure with its side chain bonded to its...

 activity, which catalyzes the cis-trans isomerization of proline

Proline

Proline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...

 peptide bonds. Although parvulin has no homology

Homology (biology)

Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...

 with larger prolyl isomerases such as cyclophilin

Cyclophilin

Cyclophilins are a family of proteins from vertebrates and other organisms that bind to cyclosporine, an immunosuppressant which is usually used to suppress rejection after internal organ transplants...

 and FKBP

FKBP

FKBP, or FK506 binding protein, is a family of proteins that have prolyl isomerase activity and are related to the cyclophilins in function, though not in amino acid sequence. FKBPs have been identified in many eukaryotes from yeast to humans and function as protein folding chaperones for proteins...

, it does share structural features with subdomains of other proteins involved in preparing secreted proteins for export from the cell

Cell (biology)

The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

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Although parvulin is as active as the larger prolyl isomerases against a short proline-containing test peptide

Peptide

Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...

, it has lower relative activity against biological substrates, possibly because the larger molecules have a higher ability to bind the substrate peptide. Parvulin itself contains proline residues and its folding

Protein folding

Protein folding is the process by which a protein structure assumes its functional shape or conformation. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil....

 can be accelerated by the presence of cyclophilin; parvulin folding can also be autocatalytic.

A eukaryotic homolog of parvulin known as Pin1 is required to execute the transition from G2 phase

G2 phase

G2 phase is the 3rd and final subphase of Interphase in the cell cycle directly preceding Mitosis. It follows the successful completion of S phase, during which the cell’s DNA is replicated...

 to M phase in the cell cycle

Cell cycle

The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...

. Absence of Pin1 activity in humans has also been implicated in the folding and processing of the amyloid precursor protein

Amyloid precursor protein

Amyloid precursor protein is an integral membrane protein expressed in many tissues and concentrated in the synapses of neurons. Its primary function is not known, though it has been implicated as a regulator of synapse formation, neural plasticity and iron export...

, whose degradation product is the cytotoxic peptide amyloid beta

Amyloid beta

Amyloid beta is a peptide of 36–43 amino acids that is processed from the Amyloid precursor protein. While it is most commonly known in association with Alzheimer's disease, it does not exist specifically to cause disease...

 implicated in Alzheimer's disease

Alzheimer's disease

Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...

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