Ligase

In biochemistry, a ligase is an enzyme that can catalyze the joining (ligation) of two molecules by forming a new chemical bond. This is typically via hydrolysis of a small pendant chemical group on one of the molecules, typically resulting in the formation of new C-O, C-S, or C-N bonds. For example, DNA ligase can join two complementary fragments of nucleic acid by forming phosphodiester bonds, and repair single stranded breaks that arise in double stranded DNA during replication.

In general, a ligase catalyzes the following dehydration reaction, thus joining molecules A and B:

A-OH + B-H → A–B + H₂O

Nomenclature

The naming of ligases is inconsistent and so these enzymes are commonly known by several different names. Generally, the common names of ligases include the word "ligase", such as in DNA ligase, an enzyme commonly used in molecular biology laboratories to join together DNA fragments. However, many common names use the term "synthetase" or "synthase" instead, because they are used to synthesize new molecules.^[1] There are also some ligases that use the name "carboxylase" to indicate that the enzyme specifically catalyzes a carboxylation reaction.

To note: biochemical nomenclature has sometimes distinguished synthetases from synthases and sometimes treated the words as synonyms.^[2] Commonly, the two terms are used interchangeably and are both used to describe ligases.

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 includes ligases used to form carbon-nitrogen bonds (including argininosuccinate synthetase)
EC 6.4 includes ligases used to form carbon-carbon bonds, such as acetyl-CoA carboxylase
EC 6.5 includes ligases used to form phosphoric ester bonds, such as DNA ligase
EC 6.6 includes ligases used to form nitrogen-metal bonds, as in the chelatases

Membrane-associated ligases

Some ligases associate with biological membranes as peripheral membrane proteins or anchored through a single transmembrane helix,^[3] 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 (denoting an enzyme), yielding "binding enzyme".

References

^ "IntEnz - EC 6". www.ebi.ac.uk. Retrieved May 2, 2023.
^ "Synthetases - Ligases - Enzymes - Products". www.axonmedchem.com. Retrieved May 2, 2023.
^ Superfamilies of single-pass transmembrane ligases in Membranome database

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

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

v t e Enzymes: CO CS and CN ligases (EC 6.1-6.3)
6.1: Carbon-Oxygen	Aminoacyl tRNA synthetase Alanine Arginine Asparagine Aspartate Cysteine D-alanine—poly(phosphoribitol) ligase Glutamate Glutamine Glycine Histidine Isoleucine Leucine Lysine Methionine Phenylalanine Proline Serine Threonine Tryptophan Tyrosine Valine
6.2: Carbon-Sulfur	Succinyl coenzyme A synthetase Acetyl—CoA synthetase Long-chain-fatty-acid—CoA ligase
6.3: Carbon-Nitrogen	Glutamine synthetase Ubiquitin ligase Cullin Von Hippel–Lindau tumor suppressor UBE3A Mdm2 Anaphase-promoting complex UBR1 Glutathione synthetase CTP synthetase Adenylosuccinate synthase Argininosuccinate synthase Holocarboxylase synthetase GMP synthase Asparagine synthetase Carbamoyl phosphate synthetase I II Glutamate–cysteine ligase

v t e Ligases: carbon-carbon ligases (EC 6.4)
Biotin dependent carboxylation	Pyruvate carboxylase Acetyl-CoA carboxylase Propionyl-CoA carboxylase Methylcrotonyl-CoA carboxylase
Other	Polyketide synthase

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