Metalloproteins

A metalloprotein is a protein that contains one or more metals without having to be catalytically active. The metal ions in these proteins are critical for their function, structure and / or stability. Catalytically active metalloproteins are called metalloenzymes (see there). They play a crucial role in biological processes, which are among the most complex and important that occur in nature. To be mentioned here are primarily photosynthesis , respiration , the molecular reduction of oxygen, the oxidation of water and nitrogen fixation . Metalloproteins make up almost half of all naturally occurring proteins, which underlines their importance.

Importance for medicine

Metalloproteins play an important role in innumerable physiological as well as pathological processes. They therefore represent possible target structures for therapeutic intervention with pharmaceuticals . A good example of the great medical potential of metalloproteins are the "clans" of metalloproteases , which are branched into at least 54 families . As early as the early 1980s, selective inhibitors of the so-called angiotensin converting enzyme of the M2 metalloproteinase family were introduced into clinical practice for the treatment of hypertension (high blood pressure). These inhibitors prevent the formation of angiotensin II , which, because of the role of this molecule in maintaining blood pressure , results in a decrease in blood pressure. More recent clinical trials have examined - albeit with little success so far - members of the metalloprotease family M10 (with the matrix metalloproteases , MMP) for their therapeutic potential with regard to diseases as diverse as cancer or arthritis and members of the M12 family. The latter includes the group of Adamalysine , u. a. the so-called TNF convertase ADAM17, which (in inflammatory inflammatory play) diseases a role. The matrix metalloproteinases MMP9 and MMP12 may have greater potential: They seem to play a key role in chronic obstructive pulmonary disease (COPD), as it was possible to show in a preclinical animal model that the inhibition of these proteins is effective in COPD. An active ingredient from the pharmaceutical company AstraZeneca that targets these metalloproteins is currently (status: 2009) in a phase II clinical study .

Examples

• Carbonic anhydrase contains zinc and very effectively catalyzes the hydration of carbon dioxide to carbonic acid .
• Concanavalin A contains calcium and manganese and specifically binds certain types of sugar without catalyzing reactions. Without these metals, the sugar bond does not work.
• Calcium binds to calmodulin , which then activates certain enzymes through protein-protein interaction . This example illustrates the importance of calcium in signal processing in the cell .
• Vanadium is enriched in certain sea ​​squirts . This is made possible by vanadium-binding proteins, so-called vanabins , which probably also play a role in the oxygen transport of these living beings.
• The ribonucleotide reductase contains an iron complex which an adjacent radical stabilized.
• Kupferchaperon for superoxide dismutase (engl. "Copper chaperone for superoxide dismutase, CCS") is a naturally occurring in all living beings protein represented by specific protein-protein interaction of the superoxide dismutase (SOD) activated by copper ion of CCS SOD is transferred. Superoxide dismutase is a very important antioxidant for the intracellular defense against free oxygen radicals , which can be partly responsible for the development of dementia .
• Plastocyanin is another copper protein , it plays an important role in photosynthesis .
• Urease contains nickel .
• The nitrate reductase (NADH) is a molybdenum-containing vegetable enzyme which catalyzes the reduction of nitrate to nitrite catalyzed.

Individual evidence

1. ↑ Lu, Y. et al .: Design of functional metalloproteins . In: Nature . 460, No. 7257, 2009, pp. 855-862. PMID 19675646 .
2. ↑ ^{a b} Maciewicz, RA & Bertrand, CP: Metalloproteins as drug targets: are we only acessing the tip of the iceberg? . In: Nature . 460, No. 7257, 2009, S. Sponsor Feature (AstraZeneca).
3. ↑ Churg, A. et al .: Effect of an MMP-9 / MMP-12 inhibitor on smoke-induced emphysema and airway remodelling in guinea pigs . In: Thorax . 62, No. 8, 2007, pp. 706-713. PMID 17311841 .