Protein–Protein Interactions: Inhibition of Mammalian Carbonic Anhydrases I–XV by the Murine Inhibitor of Carbonic Anhydrase and Other Members of the Transferrin Family

Abstract

The murine inhibitor of carbonic anhydrase (mICA), a member of the transferrin (TF) superfamily of proteins, together with human holo- and apoTF and lactoferrin (LF) were assessed as inhibitors of all catalytically active mammalian (h = human, m = murine) CA isoforms, from CA I to CA XV. mICA was a low nanomolar to subnanomolar inhibitor of hCAs I, II, III, VA, VB, VII and mCAs XV (K(I) of 0.7-44.0 nM) and inhibited the remaining isoforms with K(I) of 185.5-469 nM. hTF, apoTF, and hLF were inhibitors of most of these CAs but with reduced efficiency compared to mICA (K(I) of 18.9-453.8 nM). Biacore surface plasmon resonance and differential scanning calorimetry experiments were also used for obtaining more insights into the interaction between these proteins, which may be useful for drug design of protein-based CA inhibitors.

How many carbonic anhydrase inhibition mechanisms exist?

“…Effective, nanomolar inhibitory activity against several CA isoforms was also reported for the protein tyrosine kinase inhibitors and clinically used drugs imatinib and nilotinib 155 , for some amino acid derivatized fullerenes 156 as well as for the murine CA inhibitor mICA, a protein belonging to the transferrin family 157 . Also in these cases the inhibition mechanism is unknown.…”

Mechanisms of Host-Pathogen Protein Complex Formation and Bacterial Immune Evasion of Streptococcus suis Protein Fhb

“…BLI Analysis of the Fhb-FH/C3b/C3d Interactions-All BLI experiments were performed in PBST on a BLItz system (ForteBio Inc.) as described previously (30). Streptavidin-coated biosensors with immobilized biotinylated Fhb-associated proteins were exposed to different concentrations of FH/C3b/C3d.…”

Thermodynamic characterization of human carbonic anhydrase VB stability and intrinsic binding of compounds

“…For example, 4-phenylacetamidomethyl-benzenesulfonamide inhibited CA VB with the K i of 8.3 nM [35], the murine inhibitor of CA (a member of the transferrin superfamily of proteins) inhibited CA VB with the K i of 22.9 nM [36]. There were also some inhibitors exhibiting micromolar affinities, for example, tricyclic sulfonamides incorporating benzothiopyrano [4,3-c]pyrazole and pyridothiopyrano [4,3-c]pyrazole inhibited CA VB with the K i of 1072-3270 nM [37], C-cinnamoyl glycosides incorporating phenol moiety exhibited the K i toward CA VB from 4 to [100 lM [38].…”