Peng Z, Merz K M, Banci L
Department of Chemistry, Pennsylvania State University, University Park 16802.
Proteins. 1993 Oct;17(2):203-16. doi: 10.1002/prot.340170209.
Computer simulation techniques are used to address the question of how cyanide and related ions interact with human carbonic anhydrase II (HCAII). Spectroscopic results have suggested that cyanide is coordinated with the zinc ion, while recent X-ray results suggest that the cyanide ion is noncovalently associated with the zinc-water or zinc-hydroxide form of the enzyme. We have carried out simulations on three models in an attempt to shed light on why the spectroscopic and X-ray results differ. The first model we studied (Model I) has cyanide directly coordinated to the zinc ion, the second has it noncovalently interacting with the zinc-hydroxide (high pH) form of the enzyme (Model II), and the third has cyanide noncovalently interacting with the zinc-water (low pH) form of the enzyme (Model III). None of these models is satisfactory in explaining the available structural data obtained from X-ray crystallography. This leads us to propose an alternative model, in which HCAII hydrates HCN to form an OH-/HCN complex coordinated to the Zn ion. Ab initio calculations are consistent with this model. Based on these results we are able to explain the observed crystallographic behavior of cyanate and, by inference, thiocyanate.
计算机模拟技术被用于解决氰化物及相关离子如何与人类碳酸酐酶II（HCAII）相互作用的问题。光谱学结果表明氰化物与锌离子配位，而最近的X射线结果表明氰离子与酶的锌-水或锌-氢氧化物形式非共价结合。我们对三种模型进行了模拟，试图阐明光谱学和X射线结果为何不同。我们研究的第一个模型（模型I）中氰化物直接与锌离子配位，第二个模型中它与酶的锌-氢氧化物（高pH）形式非共价相互作用（模型II），第三个模型中氰化物与酶的锌-水（低pH）形式非共价相互作用（模型III）。这些模型都无法令人满意地解释从X射线晶体学获得的现有结构数据。这促使我们提出一个替代模型，其中HCAII使HCN水合形成与锌离子配位的OH⁻/HCN复合物。从头算计算与该模型一致。基于这些结果，我们能够解释所观察到的氰酸盐的晶体学行为，并由此推断硫氰酸盐的行为。
