Hydramacin-1 is a type of
antimicrobial
An antimicrobial is an agent that kills microorganisms or stops their growth. Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example, antibiotics are used against bacteria, and antifungals ar ...
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
. It was first isolated and reproduced in 2008 from cells of the freshwater
hydroid ''
Hydra
Hydra generally refers to:
* Lernaean Hydra, a many-headed serpent in Greek mythology
* ''Hydra'' (genus), a genus of simple freshwater animals belonging to the phylum Cnidaria
Hydra or The Hydra may also refer to:
Astronomy
* Hydra (constel ...
''. Only around 60
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
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 may int ...
, 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.
Gram-positive bacte ...
and
Gram-negative
Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...
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 gro ...
''. 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 one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
cells of the
cnidaria
Cnidaria () is a phylum under kingdom Animalia containing over 11,000 species of aquatic animals found both in freshwater and marine environments, predominantly the latter.
Their distinguishing feature is cnidocytes, specialized cells that th ...
n ''
Hydra
Hydra generally refers to:
* Lernaean Hydra, a many-headed serpent in Greek mythology
* ''Hydra'' (genus), a genus of simple freshwater animals belonging to the phylum Cnidaria
Hydra or The Hydra may also refer to:
Astronomy
* Hydra (constel ...
'', a small (almost-microscopic) freshwater animal related to
coral
Corals are marine invertebrates within the class Anthozoa of the phylum Cnidaria. They typically form compact colonies of many identical individual polyps. Coral species include the important reef builders that inhabit tropical oceans and sec ...
s,
sea anemone
Sea anemones are a group of predation, predatory marine invertebrates of the order (biology), order Actiniaria. Because of their colourful appearance, they are named after the ''Anemone'', a terrestrial flowering plant. Sea anemones are classifi ...
s and
jellyfish
Jellyfish and sea jellies are the informal common names given to the medusa-phase of certain gelatinous members of the subphylum Medusozoa, a major part of the phylum Cnidaria. Jellyfish are mainly free-swimming marine animals with umbrella- ...
.
Like other members of the
Phylum
In biology, a phylum (; plural: phyla) is a level of classification or taxonomic rank below kingdom and above class. Traditionally, in botany the term division has been used instead of phylum, although the International Code of Nomenclature f ...
Cnidaria
Cnidaria () is a phylum under kingdom Animalia containing over 11,000 species of aquatic animals found both in freshwater and marine environments, predominantly the latter.
Their distinguishing feature is cnidocytes, specialized cells that th ...
, ''Hydra'' possesses specialized defensive epithelial cells called
cnidocyte
A cnidocyte (also known as a cnidoblast or nematocyte) is an explosive cell containing one large secretory organelle called a cnidocyst (also known as a cnida () or nematocyst) that can deliver a sting to other organisms. The presence of this ce ...
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 (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
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; how ...
(
Pet32a) which was inserted in the bacteria ''
Escherichia coli
''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...
'', 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. The data, typically obtained by X-ray crystallography, NMR spectroscopy, or, increasingly, cry ...
.
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 hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
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 physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water.
Hydrophobic molecules tend to be nonpolar and, th ...
(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 parasitic or predatory worms that comprise the subclass Hirudinea within the phylum Annelida. They are closely related to the oligochaetes, which include the earthworm, and like them have soft, muscular segmented bodie ...
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 Scorpiones. They have eight legs, and are easily recognized by a pair of grasping pincers and a narrow, segmented tail, often carried in a characteristic forward curve over the back and always end ...
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. The data, typically obtained by X-ray crystallography, NMR spectroscopy, or, increasingly, cry ...
, including sequence and 3-dimensional structural information.
Hydramacin-1 (2K35) at the OCA
Antibiotics
Proteins