TY - JOUR
T1 - Enzymes for carbon sequestration
T2 - Neutron crystallographic studies of carbonic anhydrase
AU - Fisher, S. Z.
AU - Kovalevsky, A. Y.
AU - Domsic, J.
AU - Mustyakimov, M.
AU - Silverman, D. N.
AU - McKenna, R.
AU - Langan, P.
PY - 2010/11
Y1 - 2010/11
N2 - Carbonic anhydrase (CA) is a ubiquitous metalloenzyme that catalyzes the reversible hydration of CO2 to form HCO3 - and H+ using a Zn-hydroxide mechanism. The first part of catalysis involves CO2 hydration, while the second part deals with removing the excess proton that is formed during the first step. Proton transfer (PT) is thought to occur through a well ordered hydrogen-bonded network of waters that stretches from the metal center of CA to an internal proton shuttle, His64. These waters are oriented and ordered through a series of hydrogen-bonding interactions to hydrophilic residues that line the active site of CA. Neutron studies were conducted on wild-type human CA isoform II (HCA II) in order to better understand the nature and the orientation of the Zn-bound solvent (ZS), the charged state and conformation of His64, the hydrogen-bonding patterns and orientations of the water molecules that mediate PT and the ionization of hydrophilic residues in the active site that interact with the water network. Several interesting and unexpected features in the active site were observed which have implications for how PT proceeds in CA.
AB - Carbonic anhydrase (CA) is a ubiquitous metalloenzyme that catalyzes the reversible hydration of CO2 to form HCO3 - and H+ using a Zn-hydroxide mechanism. The first part of catalysis involves CO2 hydration, while the second part deals with removing the excess proton that is formed during the first step. Proton transfer (PT) is thought to occur through a well ordered hydrogen-bonded network of waters that stretches from the metal center of CA to an internal proton shuttle, His64. These waters are oriented and ordered through a series of hydrogen-bonding interactions to hydrophilic residues that line the active site of CA. Neutron studies were conducted on wild-type human CA isoform II (HCA II) in order to better understand the nature and the orientation of the Zn-bound solvent (ZS), the charged state and conformation of His64, the hydrogen-bonding patterns and orientations of the water molecules that mediate PT and the ionization of hydrophilic residues in the active site that interact with the water network. Several interesting and unexpected features in the active site were observed which have implications for how PT proceeds in CA.
UR - http://www.scopus.com/inward/record.url?scp=78049461184&partnerID=8YFLogxK
U2 - 10.1107/S0907444910019700
DO - 10.1107/S0907444910019700
M3 - Article
C2 - 21041933
AN - SCOPUS:78049461184
SN - 0907-4449
VL - 66
SP - 1178
EP - 1183
JO - Acta Crystallographica Section D: Biological Crystallography
JF - Acta Crystallographica Section D: Biological Crystallography
IS - 11
ER -