A catalytic triad refers to the three 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...

 residues found inside the active site

Active site

In biology the active site is part of an enzyme where substrates bind and undergo a chemical reaction. The majority of enzymes are proteins but RNA enzymes called ribozymes also exist. The active site of an enzyme is usually found in a cleft or pocket that is lined by amino acid residues that...

 of certain protease

Protease

A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....

 enzymes: serine

Serine

Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...

 (S), aspartate (D), and histidine

Histidine

Histidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...

 (H). They work together to break peptide bonds on polypeptides. In general terms, catalytic triad can refer to any set of three residues that function together and are directly involved in catalysis

Catalysis

Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....

. Because enzymes fold into complex three-dimensional shapes, the residues of a catalytic triad can be far from each other in the primary structure

Primary structure

The primary structure of peptides and proteins refers to the linear sequence of its amino acid structural units. The term "primary structure" was first coined by Linderstrøm-Lang in 1951...

; however, they are brought close together in the tertiary structure

Tertiary structure

In biochemistry and molecular biology, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates.-Relationship to primary structure:...

 - the macromolecular

Macromolecule

A macromolecule is a very large molecule commonly created by some form of polymerization. In biochemistry, the term is applied to the four conventional biopolymers , as well as non-polymeric molecules with large molecular mass such as macrocycles...

 3-dimensional unit.

Example

An example of a catalytic triad is present in chymotrypsin

Chymotrypsin

Chymotrypsin is a digestive enzyme that can perform proteolysis. Chymotrypsin preferentially cleaves peptide amide bonds where the carboxyl side of the amide bond is a tyrosine, tryptophan, or phenylalanine. These amino acids contain an aromatic ring in their sidechain that fits into a...

, wherein the triad (on the enzyme) consists of S195 (that is, the serine found at residue 195 in the protein sequence), D102 and H57. In essence, S195 binds to the substrate

Substrate (biochemistry)

In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...

 polypeptide to the side of a phenylalanine

Phenylalanine

Phenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...

, tryptophan

Tryptophan

Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...

, or tyrosine

Tyrosine

Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...

 residue closer to the C-terminus, holding it in place. D102 and H57 then hydrolyze the bond. This takes place in several steps.

1. Upon binding of the target protein, the carboxylic group (-COOH) on D102 forms a low-barrier hydrogen bond
   Low-barrier hydrogen bond
   A Low-barrier hydrogen bond or LBHB is a special type of hydrogen bond. This type of bond is especially strong because the distance between acceptor and donor is especially short. In regular hydrogen bonds the hydrogen ion clearly belongs to one of the heteroatoms...
   
    with H57, increasing the pKa
   PKA
   PKA, pKa, or other similar variations may stand for:* pKa, the symbol for the acid dissociation constant at logarithmic scale* Protein kinase A, a class of cAMP-dependent enzymes* Pi Kappa Alpha, the North-American social fraternity...
   
    of its imidazole nitrogen from 7 to about 12. This allows H57 to act as a powerful general base, and deprotonate S195.
2. The deprotonated S195 serves as a nucleophile
   Nucleophile
   A nucleophile is a species that donates an electron-pair to an electrophile to form a chemical bond in a reaction. All molecules or ions with a free pair of electrons can act as nucleophiles. Because nucleophiles donate electrons, they are by definition Lewis bases.Nucleophilic describes the...
   
   , attacking the carbonyl carbon on the C-terminal side of the residue and forcing the carbonyl oxygen to accept an electron, and transforming the sp2 carbon into a tetrahedral intermediate. This intermediate is stabilized by an oxanion hole
   Oxanion hole
   An oxyanion hole is a pocket in the structure of an enzyme which stabilizes a deprotonated oxygen or alkoxide, often by placing it close to positively charged residues...
   
   , which also involves S195.
3. Collapse of this intermediate back to a carbonyl causes H57 to donate its proton to the nitrogen attached to the alpha carbon. The nitrogen and the attached peptide fragment (c-terminal to the F W or Y residue) leave by diffusion.
4. A water molecule then donates a proton to H57 and the remaining OH- attacks the carbonyl carbon, forming another tetrahedral intermediate. The OH is a poorer leaving group
   Leaving group
   In chemistry, a leaving group is a molecular fragment that departs with a pair of electrons in heterolytic bond cleavage. Leaving groups can be anions or neutral molecules. Common anionic leaving groups are halides such as Cl−, Br−, and I−, and sulfonate esters, such as para-toluenesulfonate...
   
    than the C-terminal fragment, so, when the tetrahedral intermediate collapses again, S195 leaves and regains a proton from H57.
5. The cleaved peptide, now with a carboxyl end, leaves by diffusion.

Amino acid sequence, histidine 57

For three example proteases, chymotrypsin A (cow), trypsin (cow), and elastase (pig), the amino acid residues are listed in the following table; the (vertical column)-histidine 57, is coded as capital H:
(see: Sequence of proteases - chymotrypsin A - trypsin - elastase

Sequence of proteases - chymotrypsin A - trypsin - elastase

In the catalytic triad of chymotrypsin, trypsin, and elastase, the three proteases function at three important molecular 'cutting' points. The sites are at amino acid residues of: histidine 57, aspartic acid 102, and serine 195....

)

A few sections are shown as very similar, and likewise sections that are quite dissimilar-(the sections away from the "active 3-dimensional site"). From the residues 46-99A, the most common area is from residue 46 to 58, one residue past residue Histidine 57; it is even more similar, from the residues 51-58.

x	46-50	51 - 55	56,57-60	65	65A 66-70
C	LINEN	WVVTA	AHCGV	TTSDV	'VVAGEFD
T	LINSQ	WVVSA	AHCYK	SGIQV	RL'`GQDN
E	LIRQN	WVMTA	AHCVD	RELTF	RVVVGEHN

-

x	73-75-80	85	90	95	96-99A
C	QGSSSEKI	QKLKI	AKVFK	NSKYN	SLTI'
T	INVVEGNQ	QFISA	SKSIV	HPSYN	SNTL'
E	LNQNNGTE	QYVGV	QKIVV	HPYWN	TDDVA