The catalytic mechanism of human carbonic anhydrase C: Inhibition of CO2 hydration and ester hydrolysis by HCO−3

Steiner, Håkan; Jonsson, Bengt‐Harald; Lindskog, Sven

doi:10.1016/0014-5793(76)80006-3

Cited by 52 publications

(28 citation statements)

References 14 publications

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“…The values determined for Cab are the first kinetic parameters reported for a prokaryotic ␤ carbonic anhydrase. Among the prokaryotic carbonic anhydrases that have been kinetically characterized, the N. gonorrhoeae ␣-class enzyme (13) has the highest k cat value and is as catalytically efficient (k cat /K m ) as the high-activity human isozyme, CA II (29,52). The K m values for CO 2 for the ␣ and ␥ prokaryotic carbonic anhydrases (1,13) are over fivefold greater than that of Cab, suggesting that Cab may have a physiological role distinct from those of the prokaryotic ␣-and ␥-class enzymes.…”

Section: Resultsmentioning

confidence: 99%

A Plant-Type (β-Class) Carbonic Anhydrase in the Thermophilic MethanoarchaeonMethanobacterium thermoautotrophicum

1999

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Carbonic anhydrase, a zinc enzyme catalyzing the interconversion of carbon dioxide and bicarbonate, is nearly ubiquitous in the tissues of highly evolved eukaryotes. Here we report on the first known plant-type (β-class) carbonic anhydrase in the archaea. TheMethanobacterium thermoautotrophicum ΔH cabgene was hyperexpressed in Escherichia coli, and the heterologously produced protein was purified 13-fold to apparent homogeneity. The enzyme, designated Cab, is thermostable at temperatures up to 75°C. No esterase activity was detected withp-phenylacetate as the substrate. The enzyme is an apparent tetramer containing approximately one zinc per subunit, as determined by plasma emission spectroscopy. Cab has a CO2 hydration activity with a k cat of 1.7 × 104 s−1 and Km for CO2 of 2.9 mM at pH 8.5 and 25°C. Western blot analysis indicates that Cab (β class) is expressed in M. thermoautotrophicum; moreover, a protein cross-reacting to antiserum raised against the γ carbonic anhydrase fromMethanosarcina thermophila was detected. These results show that β-class carbonic anhydrases extend not only into theArchaea domain but also into the thermophilic prokaryotes.

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Section: Resultsmentioning

confidence: 99%

A Plant-Type (β-Class) Carbonic Anhydrase in the Thermophilic MethanoarchaeonMethanobacterium thermoautotrophicum

1999

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“…Although the orientation of the bound bicarbonate is somewhat different in each of these examples, in all three cases the binding of bicarbonate displaces the deep water. The dissociation constant of bicarbonate at the active site of HCA II is estimated near 100 mM by 13 C NMR measurements (26) with a similar K i value estimated by inhibition by bicarbonate of the esterase capacity of HCA II (27). The value of K m for dehydration is 32 mM (22), and concentration of bicarbonate in plasma is near 24 mM.…”

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confidence: 81%

A Short, Strong Hydrogen Bond in the Active Site of Human Carbonic Anhydrase II

Avvaru¹,

Kim

Sippel³

et al. 2009

Biochemistry

139

150

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The crystal structure of human carbonic anhydrase II (HCA II) obtained at 0.9 Å resolution reveals that a water molecule, termed deep water, Dw, and bound in a hydrophobic pocket of the active site forms a short, strong hydrogen bond with the zinc-bound solvent molecule, a conclusion based on the observed oxygen-oxygen distance of 2.45 Å. This water structure has similarities with hydrated hydroxide found in crystals of certain inorganic complexes. The energy required to displace Dw contributes in significant part to the weak binding of CO2 in the enzyme-substrate complex, a weak binding that enhances kcat for the conversion of CO2 into bicarbonate. In addition, this short, strong hydrogen bond is expected to contribute to the low pKa of the zinc-bound water and to promote proton transfer in catalysis.

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“…The catalytic mechanism of Cam appears to resemble that of the α class human isozymes [58]. The K m value for CO 2 is slightly higher (1.8‐fold) than that of the α class human CA II [142,143] but is nearly six times greater than that of the β class pea enzyme [48] (Table 1). The k cat and catalytic efficiency ( k cat / K m ) for Cam are approximately 10–100‐fold less than the eukaryotic β and α class enzymes, respectively (Table 1).…”

Section: Properties Of Isolated Carbonic Anhydrases From the Archaeamentioning

confidence: 92%

Prokaryotic carbonic anhydrases

Smith¹,

Ferry²

2000

FEMS Microbiol Rev

602

387

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Carbonic anhydrases catalyze the reversible hydration of CO(2) [CO(2)+H(2)Oright harpoon over left harpoon HCO(3)(-)+H(+)]. Since the discovery of this zinc (Zn) metalloenzyme in erythrocytes over 65 years ago, carbonic anhydrase has not only been found in virtually all mammalian tissues but is also abundant in plants and green unicellular algae. The enzyme is important to many eukaryotic physiological processes such as respiration, CO(2) transport and photosynthesis. Although ubiquitous in highly evolved organisms from the Eukarya domain, the enzyme has received scant attention in prokaryotes from the Bacteria and Archaea domains and has been purified from only five species since it was first identified in Neisseria sicca in 1963. Recent work has shown that carbonic anhydrase is widespread in metabolically diverse species from both the Archaea and Bacteria domains indicating that the enzyme has a more extensive and fundamental role in prokaryotic biology than previously recognized. A remarkable feature of carbonic anhydrase is the existence of three distinct classes (designated alpha, beta and gamma) that have no significant sequence identity and were invented independently. Thus, the carbonic anhydrase classes are excellent examples of convergent evolution of catalytic function. Genes encoding enzymes from all three classes have been identified in the prokaryotes with the beta and gamma classes predominating. All of the mammalian isozymes (including the 10 human isozymes) belong to the alpha class; however, only nine alpha class carbonic anhydrase genes have thus far been found in the Bacteria domain and none in the Archaea domain. The beta class is comprised of enzymes from the chloroplasts of both monocotyledonous and dicotyledonous plants as well as enzymes from phylogenetically diverse species from the Archaea and Bacteria domains. The only gamma class carbonic anhydrase that has thus far been isolated and characterized is from the methanoarchaeon Methanosarcina thermophila. Interestingly, many prokaryotes contain carbonic anhydrase genes from more than one class; some even contain genes from all three known classes. In addition, some prokaryotes contain multiple genes encoding carbonic anhydrases from the same class. The presence of multiple carbonic anhydrase genes within a species underscores the importance of this enzyme in prokaryotic physiology; however, the role(s) of this enzyme is still largely unknown. Even though most of the information known about the function(s) of carbonic anhydrase primarily relates to its role in cyanobacterial CO(2) fixation, the prokaryotic enzyme has also been shown to function in cyanate degradation and the survival of intracellular pathogens within their host. Investigations into prokaryotic carbonic anhydrase have already led to the identification of a new class (gamma) and future research will undoubtedly reveal novel functions for carbonic anhydrase in prokaryotes.

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The catalytic mechanism of human carbonic anhydrase C: Inhibition of CO₂ hydration and ester hydrolysis by HCO⁻₃

Cited by 52 publications

References 14 publications

A Plant-Type (β-Class) Carbonic Anhydrase in the Thermophilic MethanoarchaeonMethanobacterium thermoautotrophicum

A Plant-Type (β-Class) Carbonic Anhydrase in the Thermophilic MethanoarchaeonMethanobacterium thermoautotrophicum

A Short, Strong Hydrogen Bond in the Active Site of Human Carbonic Anhydrase II

Prokaryotic carbonic anhydrases

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