HEPN domain
Encyclopedia
In molecular biology, the HEPN domain (higher eukaryotes and prokaryotes nucleotide
-binding domain
) is a region of approximately 110 amino acids found in the C terminus of sacsin, a chaperonin
implicated in an early-onset neurodegenerative disease in human, and in many bacterial and archeabacterial protein
s. There are three classes of proteins with HEPN domains:
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
-binding domain
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...
) is a region of approximately 110 amino acids found in the C terminus of sacsin, a chaperonin
Chaperonin
Chaperonins are proteins that fold and unfold other proteins. Newly made proteins usually must fold from a linear chain of amino acids into a three-dimensional form. Chaperonins belong to a large class of molecules that assist protein folding, called molecular chaperones...
implicated in an early-onset neurodegenerative disease in human, and in many bacterial and archeabacterial protein
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...
s. There are three classes of proteins with HEPN domains:
- Single-domain HEPN proteinsProteinProteins 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...
found in many bacteria.
- Two-domain proteins with N-terminal nucleotidyltransferaseNucleotidyltransferaseNucleotidyltransferases are transferase enzymes of phosphorus-containing groups, e.g., substituents of nucleotidylic acids or simply nucleoside monophosphates...
(NT) and C- terminal HEPN domainsProtein domainA 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...
. This N-terminal NT domain belongs to a large family of NTs, which includes several classes of enzymeEnzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s that are responsible for some types of bacterialBacteriaBacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
resistance to aminoglycosides. These enzymes deactivate various antibioticAntibioticAn antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
s by transferring a nucleotidyl group to the drug.
- A multidomain sacsin protein in genomes of fishFishFish are a paraphyletic group of organisms that consist of all gill-bearing aquatic vertebrate animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish, as well as various extinct related groups...
and mammalMammalMammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s. The HEPN domain is located at the C terminus of the protein, directly after the DnaJ domain. The crystal structureCrystal structureIn mineralogy and crystallography, crystal structure is a unique arrangement of atoms or molecules in a crystalline liquid or solid. A crystal structure is composed of a pattern, a set of atoms arranged in a particular way, and a lattice exhibiting long-range order and symmetry...
of the HEPN domain from the TM0613 protein of ThermotogaThermotogaThermotoga is a genus of the phylum Thermotogae. Members of Thermotoga are hyperthermophilic bacteria whose cell is wrapped in an unique sheath-like outer membrane, called a "toga"....
maritima indicates that it is structurally similar to the C-terminal all-alpha-helical domain of kanamycinKanamycinKanamycin sulfate is an aminoglycoside antibiotic, available in oral, intravenous, and intramuscular forms, and used to treat a wide variety of infections. Kanamycin is isolated from Streptomyces kanamyceticus.-Mechanism:...
nucleotidyltransferases (KNTases). It is composed of five alpha helices, three of which form an up- and-down helical bundle, with a pair of short helicesAlpha helixA 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...
on the side. The distant structural similarity suggests that the HEPN domain might be involved in nucleotide binding.