Hydramacin-1
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Hydramacin-1 is a type of
antimicrobial An antimicrobial is an agent that kills microorganisms (microbicide) or stops their growth (bacteriostatic agent). Antimicrobial medicines can be grouped according to the microorganisms they are used to treat. For example, antibiotics are used aga ...
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
. It was first isolated and reproduced in 2008 from cells of the freshwater hydroid '' Hydra''. Only around 60
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
s long, the protein is unique both in amino acid sequence and
tertiary structure Protein tertiary structure is the three-dimensional shape of a protein. The tertiary structure will have a single polypeptide chain "backbone" with one or more protein secondary structures, the protein domains. Amino acid side chains and the ...
, prompting its classification in a new family of proteins, the macins. The protein's unusual structure is most likely a reason for the compound's potent antimicrobial qualities. Antimicrobial tests determined that the protein has an antibacterial effect against both
Gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. The Gram stain is ...
and
Gram-negative Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelope consists ...
bacteria. This potent antibacterial activity extended to known multi-resistant strains of pathogenic bacteria, such as those of ''
Klebsiella oxytoca ''Klebsiella oxytoca'' is a Gram-negative, rod-shaped bacterium that is closely related to '' K. pneumoniae'', from which it is distinguished by being indole-positive; it also has slightly different growth characteristics in that it is able to gr ...
''. Functionally, the protein causes bacterial cells to clump together and aggregate, changing the morphology of the bacterial aggregations it creates. This results in a disruption of the structure of the bacterial membrane. Hydramacin-1 was first isolated from
epithelial Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...
cells of the
cnidaria Cnidaria ( ) is a phylum under kingdom Animalia containing over 11,000 species of aquatic invertebrates found both in fresh water, freshwater and marine environments (predominantly the latter), including jellyfish, hydroid (zoology), hydroids, ...
n '' Hydra'', a small (almost-microscopic) freshwater animal related to
coral Corals are colonial marine invertebrates within the subphylum Anthozoa of the phylum Cnidaria. They typically form compact Colony (biology), colonies of many identical individual polyp (zoology), polyps. Coral species include the important Coral ...
s,
sea anemone Sea anemones ( ) are a group of predation, predatory marine invertebrates constituting the order (biology), order Actiniaria. Because of their colourful appearance, they are named after the ''Anemone'', a terrestrial flowering plant. Sea anemone ...
s and
jellyfish Jellyfish, also known as sea jellies or simply jellies, are the #Life cycle, medusa-phase of certain gelatinous members of the subphylum Medusozoa, which is a major part of the phylum Cnidaria. Jellyfish are mainly free-swimming marine animal ...
. Like other members of the
Phylum In biology, a phylum (; : phyla) is a level of classification, or taxonomic rank, that is below Kingdom (biology), kingdom and above Class (biology), class. Traditionally, in botany the term division (taxonomy), division has been used instead ...
Cnidaria Cnidaria ( ) is a phylum under kingdom Animalia containing over 11,000 species of aquatic invertebrates found both in fresh water, freshwater and marine environments (predominantly the latter), including jellyfish, hydroid (zoology), hydroids, ...
, ''Hydra'' possesses specialized defensive epithelial cells called
cnidocyte A cnidocyte (also known as a cnidoblast) is a type of cell containing a large secretory organelle called a ''cnidocyst'', that can deliver a sting to other organisms as a way to capture prey and defend against predators. A cnidocyte explosively ...
s that shoot
toxic Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...
barbs into organisms they come in physical contact with. German researchers managed to isolate the
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
that coded for the production of the protein from the ''Hydra'' genome in 2008. The gene was transferred and cloned in a
plasmid A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria and ...
( Pet32a) which was inserted in the bacteria ''
Escherichia coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...
'', a standard method of replicating a protein isolated from a much larger organism. The three-dimensional structure of the resulting protein was then determined by NMR spectroscopy and is now published online by the
Protein Data Bank The Protein Data Bank (PDB) is a database for the three-dimensional structural data of large biological molecules such as proteins and nucleic acids, which is overseen by the Worldwide Protein Data Bank (wwPDB). This structural data is obtained a ...
. Hydramacin-1 is a single-chain protein composed of sixty
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
s. It is a unique combination of amino acids on the surface of the molecule that gives the protein its potent antimicrobial qualities. This specialized part of the protein tertiary structure, a positively charged belt in between two
hydrophobic In chemistry, hydrophobicity is the chemical property of a molecule (called a hydrophobe) that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, thu ...
(and ionically inert) regions, has been suggested as the trigger for bacterial aggregation influence by the protein. Hydramacin-1 is different from any other antibacterial currently known, except for two proteins found in
leech Leeches are segmented parasitism, parasitic or Predation, predatory worms that comprise the Class (biology), subclass Hirudinea within the phylum Annelida. They are closely related to the Oligochaeta, oligochaetes, which include the earthwor ...
es. The researchers propose placing hydramacin-1 and the proteins from the leech in a newly designated protein family called the macins. The proteins closest in structure to the macins are a
superfamily SUPERFAMILY is a database and search platform of structural and functional annotation for all proteins and genomes. It classifies amino acid sequences into known structural domains, especially into SCOP superfamilies. Domains are functional, str ...
of proteins derived from
scorpion Scorpions are predatory arachnids of the Order (biology), order Scorpiones. They have eight legs and are easily recognized by a pair of Chela (organ), grasping pincers and a narrow, segmented tail, often carried in a characteristic forward cur ...
venom Venom or zootoxin is a type of toxin produced by an animal that is actively delivered through a wound by means of a bite, sting, or similar action. The toxin is delivered through a specially evolved ''venom apparatus'', such as fangs or a sti ...
, dubbed the scorpion oxins.


References


Bibliography

*{{cite journal, vauthors = Jung S, Dingley AJ, Augustin R, Anton-Erxleben F, Stanisak M, Gelhaus C, Gutsmann T, Hammer MU, Podschun R, Bonvin AM, Leippe M, Bosch TC, Grötzinger J , date=2009-01-16, title=Hydramacin-1, Structure and Antibacterial Activity of a Protein from the Basal Metazoan Hydra, journal=Journal of Biological Chemistry, publisher=The American Society for Biochemistry and Molecular Biology, volume=284, issue=3, pages=1896–1905, doi=10.1074/jbc.M804713200, pmid=19019828, doi-access=free


External links


Hydramacin-1 (2K35)
in the
Protein Data Bank The Protein Data Bank (PDB) is a database for the three-dimensional structural data of large biological molecules such as proteins and nucleic acids, which is overseen by the Worldwide Protein Data Bank (wwPDB). This structural data is obtained a ...
, including sequence and 3-dimensional structural information.
Hydramacin-1 (2K35) at the OCA
Antibiotics Proteins