Ligase Inhibitors
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In biochemistry, a ligase is an enzyme that can catalyze 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. This is typically via hydrolysis 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, 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 (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 This list contains a list of 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 official information is tabulat ...
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 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 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 related proteins.


Etymology and pronunciation

The word ''ligase'' uses combining forms of '' lig-'' (from the Latin 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 *
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


References


EC 6 Introduction
from the Department of Chemistry at Queen Mary, University of London {{Authority control