The thioredoxin fold is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
fold common to
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
s that catalyze
disulfide bond
In chemistry, a disulfide (or disulphide in British English) is a compound containing a functional group or the anion. The linkage is also called an SS-bond or sometimes a disulfide bridge and usually derived from two thiol groups.
In inor ...
formation and
isomer
In chemistry, isomers are molecules or polyatomic ions with identical molecular formula – that is, the same number of atoms of each element (chemistry), element – but distinct arrangements of atoms in space. ''Isomerism'' refers to the exi ...
ization. The fold is named for the canonical example
thioredoxin and is found in both
prokaryotic
A prokaryote (; less commonly spelled procaryote) is a single-celled organism whose cell lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Ancient Greek (), meaning 'before', and (), meaning 'nut' ...
and
eukaryotic
The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...
proteins. It is an example of an
alpha/beta protein fold that has
oxidoreductase
In biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule, the reductant, also called the electron donor, to another, the oxidant, also called the electron acceptor. This group of enzymes usually ut ...
activity. The fold's spatial topology consists of a four-stranded antiparallel
beta sheet
The beta sheet (β-sheet, also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a gene ...
sandwiched between three
alpha helices
An alpha helix (or α-helix) is a sequence of amino acids in a protein that are twisted into a coil (a helix).
The alpha helix is the most common structural arrangement in the secondary structure of proteins. It is also the most extreme type of l ...
. The strand topology is 2134 with 3 antiparallel to the rest.
Sequence conservation
Despite sequence variability in many regions of the fold, thioredoxin proteins share a common
active site
In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate, the ''binding s ...
sequence with two reactive
cysteine
Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...
residues: Cys-X-Y-Cys, where X and Y are often but not necessarily
hydrophobic
In chemistry, hydrophobicity is the chemical property of a molecule (called a hydrophobe) that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water.
Hydrophobic molecules tend to be nonpolar and, thu ...
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
s. The reduced form of the protein contains two free
thiol
In organic chemistry, a thiol (; ), or thiol derivative, is any organosulfur compound of the form , where R represents an alkyl or other organic substituent. The functional group itself is referred to as either a thiol group or a sulfhydryl grou ...
groups at the cysteine residues, whereas the oxidized form contains a disulfide bond between them.
Disulfide bond formation
Different thioredoxin fold-containing proteins vary greatly in their reactivity and in the
pKa of their free thiols, which derives from the ability of the overall protein structure to stabilize the activated
thiolate. Although the structure is fairly consistent among proteins containing the thioredoxin fold, the pKa is extremely sensitive to small variations in structure, especially in the placement of
protein backbone atoms near the first cysteine.
Examples
Human proteins containing this domain include:
*
DNAJC10
*
ERP70
*
GLRX3
*
P4HB;
PDIA2;
PDIA3;
PDIA4;
PDIA5;
PDIA6 (P5);
PDILT
*
QSOX1;
QSOX2
*
STRF8
*
TXN;
TXN2;
TXNDC1;
TXNDC10;
TXNDC11;
TXNDC13;
TXNDC14;
TXNDC15;
TXNDC16;
TXNDC2;
TXNDC3;
TXNDC4;
TXNDC5;
TXNDC6;
TXNDC8;
TXNL1;
TXNL3
References
*
External links
SCOP thioredoxin superfamilyCATH glutaredoxin topology
{{DEFAULTSORT:Thioredoxin Fold
Protein domains
Protein folds
Protein superfamilies