6G4T

The crystal structure of uninhibited C183S/C217S mutant of human CA VII

Summary for 6G4T

• Entry DOI: 10.2210/pdb6g4t/pdb
• Related: 3ML5
• Descriptor: Carbonic anhydrase 7, ZINC ION (3 entities in total)
• Functional Keywords: enzyme, catalytic mechanism, lyase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 30991.10

Authors

Di Fiore, A.,D'Ambrosio, K.,De Simone, G. (deposition date: 2018-03-28, release date: 2018-06-06, Last modification date: 2024-10-23)

Primary citation

Buonanno, M.,Di Fiore, A.,Langella, E.,D'Ambrosio, K.,Supuran, C.T.,Monti, S.M.,De Simone, G.
The Crystal Structure of a hCA VII Variant Provides Insights into the Molecular Determinants Responsible for Its Catalytic Behavior.
Int J Mol Sci, 19:-, 2018

PubMed Abstract: Although important progress has been achieved in understanding the catalytic mechanism of Carbonic Anhydrases, a detailed picture of all factors influencing the catalytic efficiency of the various human isoforms is still missing. In this paper we report a detailed structural study and theoretical pKa calculations on a hCA VII variant. The obtained data were compared with those already known for another thoroughly investigated cytosolic isoform, hCA II. Our structural studies show that in hCA VII the network of ordered water molecules, which connects the zinc bound solvent molecule to the proton shuttle His64, is altered compared to hCA II, causing a reduction of the catalytic efficiency. Theoretical calculations suggest that changes in solvent network are related to the difference in pKa of the proton shuttle in the two enzymes. The residue that plays a major role in determining the diverse pKa values of the proton shuttle is the one in position four, namely His for hCA II and Gly for hCA VII. This residue is located on the protein surface, outside of the active site cavity. These findings are in agreement with our previous studies that highlighted the importance of histidines on the protein surface of hCA II (among which His4) as crucial residues for the high catalytic efficiency of this isoform.

PubMed: 29795045
DOI: 10.3390/ijms19061571

Experimental method

X-RAY DIFFRACTION (1.91 Å)