Structural Contour Map of the Iota Carbonic Anhydrase from the Diatom Thalassiosira pseudonana Using a Multiprong Approach

Abstract

Carbonic anhydrases (CAs) are a family of ubiquitous enzymes that catalyze the interconversion of CO2 and HCO3−. The “iota” class (ι-CA) was first found in the marine diatom Thalassiosira pseudonana (tpι-CA) and is widespread among photosynthetic microalgae and prokaryotes. The ι-CA has a domain COG4875 (or COG4337) that can be repeated from one to several times and resembles a calcium–calmodulin protein kinase II association domain (CaMKII-AD). The crystal structure of this domain in the ι-CA from a cyanobacterium and a chlorarachniophyte has been recently determined. However, the three-dimensional organization of the four domain-containing tpι-CA is unknown. Using biophysical techniques and 3-D modeling, we show that the homotetrameric tpι-CA in solution has a flat “drone-like” shape with a core formed by the association of the first two domains of each monomer, and four protruding arms formed by domains 3 and 4. We also observe that the short linker between domains 3 and 4 in each monomer confers high flexibility, allowing for different conformations to be adopted. We propose the possible 3-D structure of a truncated tpι-CA containing fewer domain repeats using experimental data and discuss the implications of this atypical shape on the activity and metal coordination of the ι-CA.

Five-Membered Heterocyclic Sulfonamides as Carbonic Anhydrase Inhibitors

“…The second step, which is rate limiting, regenerates the catalytically active Zn 2+ -bound hydroxide ion through a proton transfer reaction from the Zn 2+ -bound water molecule to an exogenous proton acceptor or to an active site residue, as shown in Scheme 1 [ 1 , 2 , 3 , 4 , 5 ]. These enzymes are widely distributed in nature and, nowadays, are classified in eight different genetic unrelated families, namely the α-, β-, γ-, δ-, η-, ζ-, θ and –ι classes [ 6 , 7 , 8 , 9 , 10 ]. This simple reaction plays important roles in various physiological processes, including acid-base balance, regulation of intra-/extracellular pH, metabolism and carbon dioxide transport [ 11 , 12 , 13 , 14 ].…”

Amine- and Amino Acid-Based Compounds as Carbonic Anhydrase Activators

“…The last CA family that was very recently identified is referred as ι-. Such a CA was firstly isolated from the diatom Thalassiosira pseudonana and subsequently found in algae, bacteria, and archaea [ 26 , 27 , 28 ]. From the structural view point the ι-class is unique since primary structure alignments with all CAs known to date do not show any of the amino acid residues necessary for the metal ion to be coordinated.…”

Assortment of Frontiers in Protein Science

“…The quaternary structure of the iota carbonic anhydrase (CA) from the marine diatom Thalassiosira pseudonana was modeled by Jensen et al [ 21 ]. The protein is built up from domains resembling a calcium–calmodulin protein kinase II association domain.…”