β-galactosidase is an exoglycosidase which hydrolyzes the β-glycosidic bond formed between a galactose and its organic moiety. It may also cleave fucosides and arabinosides but with much lower efficiency. It is an essential enzyme in the human body. Deficiencies in the protein can result in galactosialidosis or Morquio B syndrome. In E. coli, the lacZ gene is the structural gene for β-galactosidase; which is present as part of the inducible system lac operon which is activated in the presence of lactose when glucose level is low. β-galactosidase synthesis stops when glucose levels are sufficient.
Beta-galactosidase has many homologues based on similar sequences. A few are evolved beta-galactosidase (EBG), beta-glucosidase, 6-phospho-beta-galactosidase, beta-mannosidase, and lactase-phlorizin hydrolase. Although they may be structurally similar, they all have different functions. Beta-gal is inhibited by L-ribose, non-competitive inhibitor iodine, and competitive inhibitors phenylthyl thio-beta-D-galactoside (PETG), D-galactonolactone, isopropyl thio-beta-D-galactoside (IPTG), and galactose.
β-galactosidase is important for organisms as it is a key provider in the production of energy and a source of carbons through the break down of lactose to galactose and glucose. It is also important for the lactose intolerant community as it is responsible for making lactose-free milk and other dairy products. Many adult humans lack the lactase enzyme, which has the same function of beta-gal, so they are not able to properly digest dairy products. Beta-galactose is used in such dairy products as yogurt, sour cream, and some cheeses which are treated with the enzyme to break down any lactose before human consumption. In recent years, beta-galactosidase has been researched as a potential treatment for lactose intolerance through gene replacement therapy where it could be placed into the human DNA so individuals can break down lactose on their own.
The 1,024 amino acids of E. coli β-galactosidase were first sequenced in 1970, and its structure determined twenty-four years later in 1994. The protein is a 464-kDa homotetramer with 2,2,2-point symmetry. Each unit of β-galactosidase consists of five domains; domain 1 is a jelly-roll type barrel, domain 2 and 4 are fibronectin type III-like barrels, domain 5 a β-sandwich, while the central domain 3 is a TIM-type barrel.
The third domain contains the active site. The active site is made up of elements from two subunits of the tetramer, and disassociation of the tetramer into dimers removes critical elements of the active site. The amino-terminal sequence of β-galactosidase, the α-peptide involved in α-complementation, participates in a subunit interface. Its residues 22-31 help to stabilize a four-helix bundle which forms the major part of that interface, and residue 13 and 15 also contributing to the activating interface. These structural features provide a rationale for the phenomenon of α-complementation, where the deletion of the amino-terminal segment results in the formation of an inactive dimer.