1MUA

STRUCTURE AND ENERGETICS OF A NON-PROLINE CIS-PEPTIDYL LINKAGE IN AN ENGINEERED PROTEIN

1MUA の概要

• エントリーDOI: 10.2210/pdb1mua/pdb
• 分子名称: CARBONIC ANHYDRASE II, ZINC ION, MERCURY (II) ION, ... (4 entities in total)
• 機能のキーワード: lyase(oxo-acid)
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P00918
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29043.42

構造登録者

Nair, S.K.,Christianson, D.W. (登録日: 1993-06-18, 公開日: 1993-10-31, 最終更新日: 2024-02-14)

主引用文献

Tweedy, N.B.,Nair, S.K.,Paterno, S.A.,Fierke, C.A.,Christianson, D.W.
Structure and energetics of a non-proline cis-peptidyl linkage in a proline-202-->alanine carbonic anhydrase II variant.
Biochemistry, 32:10944-10949, 1993

PubMed Abstract: The crystal structure of a human carbonic anhydrase II (CAII) variant, cis-proline-202-->alanine (P202A), has been determined at 1.7-A resolution, indicating that the wild-type geometry, including the cis-peptidyl linkage, is retained upon substitution of proline by alanine. The CO2 hydrase activity and affinity for sulfonamide inhibitors of P202A CAII are virtually identical to those of wild type. However, the substitution of cis-alanine for cis-proline decreases the stability of the folded state by approximately 5 kcal mol-1 relative to both the unfolded state and an equilibrium intermediate in guanidine hydrochloride-induced denaturation. This destabilization can be attributed mainly to the less favorable cis/trans equilibrium of Xaa-alanine bonds compared to Xaa-proline bonds in the denatured state although other factors, including increased conformational entropy of the denatured state and decreased packing interactions in the native state, also contribute to the observed destabilization. The high catalytic activity of P202A CAII illustrates that unfavorable local conformations are nonetheless endured to satisfy the precise structural requirements of catalysis and ligand binding in the CAII active site.

PubMed: 8218160
DOI: 10.1021/bi00092a003

実験手法

X-RAY DIFFRACTION (1.7 Å)