Astacin
Encyclopedia
In molecular biology, astacin is a family of metallopeptidases. These metallopeptidases belong to the MEROPS peptidase family M12, subfamily M12A (astacin family, clan MA(M)). The protein fold
of the peptidase domain for members of this family resembles that of thermolysin
, the type example for clan MA and the predicted active site
residue
s for members of this family and thermolysin occur in the motif HEXXH.
The astacin family of metalloendopeptidases (EC 3.4.24.21) encompasses a range of proteins found in hydra to humans, in mature and developmental systems. Their functions include activation of growth
factors, degradation of polypeptides, and processing of extracellular
proteins
. The proteins are synthesised with N-terminal signal and pro-enzyme sequences, and many contain multiple domains C-terminal to the protease
domain. They are either secreted from cells, or are associated with the plasma membrane
.
The astacin molecule adopts a kidney shape, with a deep active-site cleft between its N- and C-terminal domains
. The zinc
ion, which lies at the bottom of the cleft, exhibits a unique penta-coordinated mode of binding, involving 3 histidine
residues, a tyrosine
and a water molecule (which is also bound to the carboxylate side chain
of Glu93). The N-terminal domain comprises 2 alpha-helices
and a 5-stranded beta-sheet. The overall topology of this domain is shared by the archetypal zinc-endopeptidase thermolysin. Astacin protease domains also share common features with serralysins, matrix metalloendopeptidases, and snake
venom proteases; they cleave peptide bond
s in polypeptides such as insulin
B chain
and bradykinin, and in proteins such as casein and gelatin; and they have arylamidase activity.
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....
of the peptidase domain for members of this family resembles that of thermolysin
Thermolysin
Thermolysin is a thermostable neutral metalloproteinase enzyme produced by the gram-positive bacteria Bacillus thermoproteolyticus. It requires one zinc ion for enzyme activity and four calcium ions for structural stability. Thermolysin specifically catalyzes the hydrolysis of peptide bonds...
, the type example for clan MA and the predicted 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...
residue
Residue (chemistry)
In chemistry, residue is the material remaining after a distillation or an evaporation, or to a portion of a larger molecule, such as a methyl group. It may also refer to the undesired byproducts of a reaction....
s for members of this family and thermolysin occur in the motif HEXXH.
The astacin family of metalloendopeptidases (EC 3.4.24.21) encompasses a range of proteins found in hydra to humans, in mature and developmental systems. Their functions include activation of growth
Cell growth
The term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...
factors, degradation of polypeptides, and processing of extracellular
Extracellular
In cell biology, molecular biology and related fields, the word extracellular means "outside the cell". This space is usually taken to be outside the plasma membranes, and occupied by fluid...
proteins
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
. The proteins are synthesised with N-terminal signal and pro-enzyme sequences, and many contain multiple domains C-terminal to the 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....
domain. They are either secreted from cells, or are associated with the plasma membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
.
The astacin molecule adopts a kidney shape, with a deep active-site cleft between its N- and C-terminal domains
Protein domain
A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...
. The zinc
Zinc
Zinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...
ion, which lies at the bottom of the cleft, exhibits a unique penta-coordinated mode of binding, involving 3 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...
residues, a 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...
and a water molecule (which is also bound to the carboxylate side chain
Side chain
In organic chemistry and biochemistry, a side chain is a chemical group that is attached to a core part of the molecule called "main chain" or backbone. The placeholder R is often used as a generic placeholder for alkyl group side chains in chemical structure diagrams. To indicate other non-carbon...
of Glu93). The N-terminal domain comprises 2 alpha-helices
Alpha helix
A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...
and a 5-stranded beta-sheet. The overall topology of this domain is shared by the archetypal zinc-endopeptidase thermolysin. Astacin protease domains also share common features with serralysins, matrix metalloendopeptidases, and snake
Snake
Snakes are elongate, legless, carnivorous reptiles of the suborder Serpentes that can be distinguished from legless lizards by their lack of eyelids and external ears. Like all squamates, snakes are ectothermic, amniote vertebrates covered in overlapping scales...
venom proteases; they cleave peptide bond
Peptide bond
This article is about the peptide link found within biological molecules, such as proteins. A similar article for synthetic molecules is being created...
s in polypeptides such as insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
B chain
Polymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
and bradykinin, and in proteins such as casein and gelatin; and they have arylamidase activity.
Examples
Human genes encoding proteins containing the astacin domain include:- ASTL; BMP1Bone morphogenetic protein 1Bone morphogenetic protein 1, also known as BMP1, is a protein which in humans is encoded by the BMP1 gene. There are seven isoforms of the protein created by alternate splicing.-Function:...
; MEP1AMEP1AMeprin A subunit alpha also known as endopeptidase-2 or PABA peptide hydrolase is the alpha subunit of the meprin A enzyme that in humans is encoded by the MEP1A gene...
; MEP1BMEP1BMeprin A subunit beta is a protein that in humans is encoded by the MEP1B gene.-Further reading:...
; TLL1TLL1Tolloid-like protein 1 is a protein that in humans is encoded by the TLL1 gene.-Further reading:...
; TLL2TLL2Tolloid-like protein 2 is a protein that in humans is encoded by the TLL2 gene.-Further reading:...