3MC2

Crystal Structure of the Murine Inhibitor of Carbonic Anhydrase

3MC2 の概要

• エントリーDOI: 10.2210/pdb3mc2/pdb
• 分子名称: Inhibitor of Carbonic Anhydrase (1 entity in total)
• 機能のキーワード: mica, transferrin superfamily, lyase inhibitor
• 由来する生物種: Mus musculus (mouse)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 302879.62

構造登録者

Eckenroth, B.E.,Mason, A.B.,Everse, S.J. (登録日: 2010-03-26, 公開日: 2010-07-28, 最終更新日: 2024-11-06)

主引用文献

Eckenroth, B.E.,Mason, A.B.,McDevitt, M.E.,Lambert, L.A.,Everse, S.J.
The structure and evolution of the murine inhibitor of carbonic anhydrase: A member of the transferrin superfamily.
Protein Sci., 19:1616-1626, 2010

PubMed Abstract: The original signature of the transferrin (TF) family of proteins was the ability to bind ferric iron with high affinity in the cleft of each of two homologous lobes. However, in recent years, new family members that do not bind iron have been discovered. One new member is the inhibitor of carbonic anhydrase (ICA), which as its name indicates, binds to and strongly inhibits certain isoforms of carbonic anhydrase. Recently, mouse ICA has been expressed as a recombinant protein in a mammalian cell system. Here, we describe the 2.4 Å structure of mouse ICA from a pseudomerohedral twinned crystal. As predicted, the structure is bilobal, comprised of two α-β domains per lobe typical of the other family members. As with all but insect TFs, the structure includes the unusual reverse γ-turn in each lobe. The structure is consistent with the fact that introduction of two mutations in the N-lobe of murine ICA (mICA) (W124R and S188Y) allowed it to bind iron with high affinity. Unexpectedly, both lobes of the mICA were found in the closed conformation usually associated with presence of iron in the cleft, and making the structure most similar to diferric pig TF. Two new ICA family members (guinea pig and horse) were identified from genomic sequences and used in evolutionary comparisons. Additionally, a comparison of selection pressure (dN/dS) on functional residues reveals some interesting insights into the evolution of the TF family including that the N-lobe of lactoferrin may be in the process of eliminating its iron binding function.

PubMed: 20572014
DOI: 10.1002/pro.439

実験手法

X-RAY DIFFRACTION (2.4 Å)