2010
DOI: 10.1016/j.bbapap.2009.08.003
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Proton transfer in catalysis and the role of proton shuttles in carbonic anhydrase

Abstract: The undisputed role of His64 in proton transfer during catalysis by carbonic anhydrases in the α class has raised questions concerning the details of its mechanism. The highly conserved residues Tyr7, Asn62, and Asn67 in the active-site cavity function to fine tune the properties of proton transfer by human carbonic anhydrase II (HCA II). For example, hydrophobic residues at these positions favor an inward orientation of His64 and a low pK a for its imidazole side chain. It appears that the predominant manner … Show more

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Cited by 80 publications
(78 citation statements)
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“…The values of the pK a of the zinc-bound water molecule obtained from the pH profiles of k cat exch /K eff CO2 (Figure 2) and R H2O /[E] (Supporting Information, Figure S1) were not significantly altered compared with wild type (Table 2). However, the values of the pK a of the imidazole side chain of His 64 obtained from pH profiles of R H2O /[E] were decreased slightly for the mutants (Table 2), an effect seen previously in variants of HCA II in which the orientation of the side chain of His64 was inward (20). …”
Section: Resultsmentioning
confidence: 54%
“…The values of the pK a of the zinc-bound water molecule obtained from the pH profiles of k cat exch /K eff CO2 (Figure 2) and R H2O /[E] (Supporting Information, Figure S1) were not significantly altered compared with wild type (Table 2). However, the values of the pK a of the imidazole side chain of His 64 obtained from pH profiles of R H2O /[E] were decreased slightly for the mutants (Table 2), an effect seen previously in variants of HCA II in which the orientation of the side chain of His64 was inward (20). …”
Section: Resultsmentioning
confidence: 54%
“…The Zn 2+ -bound OH À attacks the carbon of CO 2 to form HCO À 3 , and a water molecule replaces the HCO À 3 product. 113 The proton product dissociates from water and is transferred in three steps along a chain of hydrogen bonded waters to His64. 114 This protonated His64 side chain rotates to get maximally exposed to the solvent on the enzyme exterior.…”
Section: Activators Of Carbonic Anhydrasementioning
confidence: 99%
“…Conversely, the second step of the reaction consists of the regeneration of the zincbound hydroxide by means of the transfer of a proton from the zinc-bound water molecule to the external buffer. [3][4][5] This step is rate limiting and is generally assisted by a residue, which acts as proton shuttle. This residue is located in the enzyme active site and is connected to the zinc-bound water molecule through a well ordered hydrogen bonded water network.…”
mentioning
confidence: 99%
“…1,2 This catalytic reaction consists of two separate steps, described by equations (1) and (2). [3][4][5] EZn 2+ -OH -+ CO 2 …”
mentioning
confidence: 99%