BIOMAT Database Logo BIOMAT Database Logo

Neutron structure of human carbonic anhydrase II: implications for proton transfer. 2010

S Zoë Fisher, and Andrey Y Kovalevsky, and John F Domsic, and Marat Mustyakimov, and Robert McKenna, and David N Silverman, and Paul A Langan
Bioscience Division MS M888, Los Alamos National Laboratory, Los Alamos, New Mexico 87544, USA. zfisher@lanl.gov

Human carbonic anhydrase II (HCA II) catalyzes the reversible hydration of carbon dioxide to form bicarbonate and a proton. Despite many high-resolution X-ray crystal structures, mutagenesis, and kinetic data, the structural details of the active site, especially the proton transfer pathway, are unclear. A large HCA II crystal was prepared at pH 9.0 and subjected to vapor H-D exchange to replace labile hydrogens with deuteriums. Neutron diffraction studies were conducted at the Protein Crystallography Station at Los Alamos National Laboratory. The structure to 2.0 A resolution reveals several interesting active site features: (1) the Zn-bound solvent appearing to be predominantly a D(2)O molecule, (2) the orientation and hydrogen bonding pattern of solvent molecules in the active site cavity, (3) the side chain of His64 being unprotonated (neutral) and predominantly in an inward conformation pointing toward the zinc, and (4) the phenolic side chain of Tyr7 appearing to be unprotonated. The implications of these details are discussed, and a proposed mechanism for proton transfer is presented.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D009502 Neutrons Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. Neutron
D011522 Protons Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. Hydrogen Ions,Hydrogen Ion,Ion, Hydrogen,Ions, Hydrogen,Proton
D002245 Carbon Dioxide A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. Carbonic Anhydride,Anhydride, Carbonic,Dioxide, Carbon
D002384 Catalysis The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction. Catalyses
D006639 Histidine An essential amino acid that is required for the production of HISTAMINE. Histidine, L-isomer,L-Histidine,Histidine, L isomer,L-isomer Histidine
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006860 Hydrogen Bonding A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds. Hydrogen Bonds,Bond, Hydrogen,Hydrogen Bond
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships

Related Publications

S Zoë Fisher, and Andrey Y Kovalevsky, and John F Domsic, and Marat Mustyakimov, and Robert McKenna, and David N Silverman, and Paul A Langan
Identification of proton-transfer pathways in human carbonic anhydrase II.
September 2007, The journal of physical chemistry. B,
S Zoë Fisher, and Andrey Y Kovalevsky, and John F Domsic, and Marat Mustyakimov, and Robert McKenna, and David N Silverman, and Paul A Langan
Proton transfer in a Thr200His mutant of human carbonic anhydrase II.
November 2005, Proteins,
S Zoë Fisher, and Andrey Y Kovalevsky, and John F Domsic, and Marat Mustyakimov, and Robert McKenna, and David N Silverman, and Paul A Langan
Comparison of intra- and intermolecular proton transfer in human carbonic anhydrase II.
July 1994, The Journal of biological chemistry,
S Zoë Fisher, and Andrey Y Kovalevsky, and John F Domsic, and Marat Mustyakimov, and Robert McKenna, and David N Silverman, and Paul A Langan
Proton transfer from exogenous donors in catalysis by human carbonic anhydrase II.
May 2005, Archives of biochemistry and biophysics,
S Zoë Fisher, and Andrey Y Kovalevsky, and John F Domsic, and Marat Mustyakimov, and Robert McKenna, and David N Silverman, and Paul A Langan
Chemical rescue of enzymes: proton transfer in mutants of human carbonic anhydrase II.
April 2011, Journal of the American Chemical Society,
S Zoë Fisher, and Andrey Y Kovalevsky, and John F Domsic, and Marat Mustyakimov, and Robert McKenna, and David N Silverman, and Paul A Langan
Role of protein motions on proton transfer pathways in human carbonic anhydrase II.
February 2010, Biochimica et biophysica acta,
S Zoë Fisher, and Andrey Y Kovalevsky, and John F Domsic, and Marat Mustyakimov, and Robert McKenna, and David N Silverman, and Paul A Langan
The refined atomic structure of carbonic anhydrase II at 1.05 A resolution: implications of chemical rescue of proton transfer.
January 2003, Acta crystallographica. Section D, Biological crystallography,
S Zoë Fisher, and Andrey Y Kovalevsky, and John F Domsic, and Marat Mustyakimov, and Robert McKenna, and David N Silverman, and Paul A Langan
Water networks in fast proton transfer during catalysis by human carbonic anhydrase II.
January 2013, Biochemistry,
S Zoë Fisher, and Andrey Y Kovalevsky, and John F Domsic, and Marat Mustyakimov, and Robert McKenna, and David N Silverman, and Paul A Langan
Modeling the structure and proton transfer pathways of the mutant His-107-Tyr of human carbonic anhydrase II.
January 2013, Journal of molecular modeling,
S Zoë Fisher, and Andrey Y Kovalevsky, and John F Domsic, and Marat Mustyakimov, and Robert McKenna, and David N Silverman, and Paul A Langan
Proton transfer pathways in the mutant His-64-Ala of human carbonic anhydrase II.
August 2006, Biopolymers,
Copied contents to your clipboard!