In
biochemistry
Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology and ...
, a ligase is an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
that can
catalyze
Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
the joining (
ligation
Ligation may refer to:
* Ligation (molecular biology), the covalent linking of two ends of DNA or RNA molecules
* In medicine, the making of a ligature (tie)
* Chemical ligation, the production of peptides from amino acids
* Tubal ligation, a meth ...
) of two large molecules by forming a new
chemical bond
A chemical bond is a lasting attraction between atoms or ions that enables the formation of molecules and crystals. The bond may result from the electrostatic force between oppositely charged ions as in ionic bonds, or through the sharing of ...
. This is typically via
hydrolysis
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...
of a small pendant chemical group on one of the larger molecules or the enzyme catalyzing the linking together of two compounds, e.g., enzymes that catalyze joining of C-O, C-S, C-N, etc. In general, a ligase catalyzes the following reaction:
:Ab + C → A–C + b
or sometimes
:Ab + cD → A–D + b + c + d + e + f
where the lowercase letters can signify the small, dependent groups. Ligase can join two complementary fragments of nucleic acid and repair single stranded breaks that arise in double stranded DNA during replication.
Nomenclature
The common names of ligases often include the word "ligase", such as
DNA ligase
DNA ligase is a specific type of enzyme, a ligase, () that facilitates the joining of DNA strands together by catalyzing the formation of a phosphodiester bond. It plays a role in repairing single-strand breaks in duplex DNA in living organ ...
, an enzyme commonly used in molecular biology
laboratories
A laboratory (; ; colloquially lab) is a facility that provides controlled conditions in which scientific or technological research, experiments, and measurement may be performed. Laboratory services are provided in a variety of settings: physicia ...
to join together
DNA fragments. Other common names for ligases include the word "synthetase", because they are used to
synthesize new molecules.
Biochemical nomenclature has sometimes distinguished synthetases from
synthase In biochemistry, a synthase is an enzyme that catalyses a synthesis process.
Note that, originally, biochemical nomenclature distinguished synthetases and synthases. Under the original definition, synthases do not use energy from nucleoside tripho ...
s and sometimes treated the words as
synonym
A synonym is a word, morpheme, or phrase that means exactly or nearly the same as another word, morpheme, or phrase in a given language. For example, in the English language, the words ''begin'', ''start'', ''commence'', and ''initiate'' are all ...
s. Under one definition, synthases ''do not'' use energy from
nucleoside triphosphate
A nucleoside triphosphate is a nucleoside containing a nitrogenous base bound to a 5-carbon sugar (either ribose or deoxyribose), with three phosphate groups bound to the sugar. They are the molecular precursors of both DNA and RNA, which are cha ...
s (such as ATP, GTP, CTP, TTP, and UTP), whereas synthetases ''do'' use nucleoside triphosphates. It is also said that a synthase is a
lyase
In biochemistry, a lyase is an enzyme that catalyzes the breaking (an elimination reaction) of various chemical bonds by means other than hydrolysis (a substitution reaction) and oxidation, often forming a new double bond or a new ring structure. ...
(a lyase is an enzyme that catalyzes the breaking of various chemical bonds by means other than hydrolysis and oxidation, often forming a new double bond or a new ring structure) and does not require any energy, whereas a synthetase is a ligase (a ligase is an enzyme that binds two chemicals or compounds) and thus requires energy. However, the
Joint Commission on Biochemical Nomenclature
A joint or articulation (or articular surface) is the connection made between bones, ossicles, or other hard structures in the body which link an animal's skeletal system into a functional whole.Saladin, Ken. Anatomy & Physiology. 7th ed. McGraw- ...
(JCBN) dictates that "synthase" can be used with any enzyme that catalyses synthesis (whether or not it uses nucleoside triphosphates), whereas "synthetase" is to be used synonymously.
Classification
Ligases are classified as EC 6 in the
EC number classification of enzymes. Ligases can be further classified into six subclasses:
*
EC 6.1 includes ligases used to form carbon-oxygen bonds
*
EC 6.2 includes ligases used to form carbon-sulfur bonds
*
EC 6.3
This list contains a list of Enzyme Commission number, EC numbers for the sixth group, EC 6, ligases, placed in numerical order as determined by the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology. All offici ...
includes ligases used to form carbon-nitrogen bonds (including
argininosuccinate synthetase
Argininosuccinate synthase or synthetase (ASS; ) is an enzyme that catalyzes the synthesis of argininosuccinic acid, argininosuccinate from citrulline and aspartic acid, aspartate. In humans, argininosuccinate synthase is encoded by the ''ASS ...
)
*
EC 6.4 includes ligases used to form carbon-carbon bonds
*
EC 6.5 includes ligases used to form
phosphoric ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides are fa ...
bonds
*
EC 6.6 includes ligases used to form nitrogen-metal bonds, as in the
chelatase
In biochemistry, chelatases are enzymes that catalyze the insertion ("metalation") of naturally occurring tetrapyrroles. Many tetrapyrrole-based cofactors exist in nature including hemes, chlorophylls, and vitamin B12. These metallo cofactors are ...
s
Membrane-associated ligases
Some ligases associate with
biological membranes
A biological membrane, biomembrane or cell membrane is a selectively permeable membrane that separates the interior of a cell from the external environment or creates intracellular compartments by serving as a boundary between one part of the ce ...
as
peripheral membrane protein
Peripheral membrane proteins, or extrinsic membrane proteins, are membrane proteins that adhere only temporarily to the biological membrane with which they are associated. These proteins attach to integral membrane proteins, or penetrate the periph ...
s or anchored through a single
transmembrane helix
A transmembrane domain (TMD) is a membrane-spanning protein domain. TMDs generally adopt an alpha helix topological conformation, although some TMDs such as those in porins can adopt a different conformation. Because the interior of the lipid bi ...
,
Superfamilies of single-pass transmembrane ligases
in Membranome database
Membranome database provides structural and functional information about more than 6000 single-pass (bitopic) transmembrane proteins from ''Homo sapiens'', ''Arabidopsis thaliana'', ''Dictyostelium discoideum'', ''Saccharomyces cerevisiae'', '' ...
for example certain ubiquitin ligase
A ubiquitin ligase (also called an E3 ubiquitin ligase) is a protein that recruits an E2 ubiquitin-conjugating enzyme that has been loaded with ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquitin ...
related proteins.
Etymology and pronunciation
The word ''ligase'' uses combining forms of '' lig-'' (from the Latin
Latin (, or , ) is a classical language belonging to the Italic branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) around present-day Rome, but through the power of the ...
verb ''ligāre'', "to bind" or "to tie together") + ''-ase
The suffix -ase is used in biochemistry to form names of enzymes. The most common way to name enzymes is to add this suffix onto the end of the substrate, ''e.g.'' an enzyme that breaks down peroxides may be called peroxidase; the enzyme that pro ...
'' (denoting an enzyme), yielding "binding enzyme".
See also
*DNA ligase
DNA ligase is a specific type of enzyme, a ligase, () that facilitates the joining of DNA strands together by catalyzing the formation of a phosphodiester bond. It plays a role in repairing single-strand breaks in duplex DNA in living organ ...
*Nuclease
A nuclease (also archaically known as nucleodepolymerase or polynucleotidase) is an enzyme capable of cleaving the phosphodiester bonds between nucleotides of nucleic acids. Nucleases variously effect single and double stranded breaks in their ta ...
*Protease
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...
References
EC 6 Introduction
from the Department of Chemistry at Queen Mary, University of London
, mottoeng = With united powers
, established = 1785 – The London Hospital Medical College1843 – St Bartholomew's Hospital Medical College1882 – Westfield College1887 – East London College/Queen Mary College
, type = Public researc ...
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