structural studies of β-carbonic anhydrase from the green alga coccomyxa inhibitor complexes with anions and acetazolamide结构的研究β-carbonic脱水酶的绿藻coccomyxa抑制剂复合物与阴离子和乙酰唑胺.pdf

Structural Studies of b-Carbonic Anhydrase from the Green Alga Coccomyxa: Inhibitor Complexes with Anions and Acetazolamide 1 1 ¨ 1 1¤ ¨ 2 Shenghua Huang , Tobias Hainzl , Christin Grundstrom , Cecilia Forsman , Goran Samuelsson , A. Elisabeth Sauer-Eriksson1* ˚ ˚ ˚ ˚ ˚ 1 Department of Chemistry, Umea University, Umea, Sweden, 2 Department of Plant Physiology, Umea Plant Science Centre, Umea University, Umea, Sweden Abstract The b-class carbonic anhydrases (b-CAs) are widely distributed among lower eukaryotes, prokaryotes, archaea, and plants. Like all CAs, the b-enzymes catalyze an important physiological reaction, namely the interconversion between carbon dioxide and bicarbonate. In plants the enzyme plays an important role in carbon fixation and metabolism. To further explore the structure-function relationship of b-CA, we have determined the crystal structures of the photoautotroph unicellular green alga Coccomyxa b-CA in complex with five different inhibitors: acetazolamide, thiocyanate, azide, iodide, and phosphate ions. The tetrameric Coccomyxa b-CA structure is similar to other b-CAs but it has a 15 amino acid extension in the C-terminal end, which stabilizes the tetramer by strengthening the interface. Four of the five inhibitors bind in a manner similar to what is found in complexes with a-type CAs. Iodide ions, however, make contact to the zinc ion via a zinc-bound water molecule or hydroxide ion — a type of binding mode not previously observed in any CA. Binding of inhibitors to Coccomyxa b-CA is media