Karlin S, Zhu Z Y
Department of Mathematics, Stanford University, Stanford, CA 94305-2125, USA.
Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14231-6. doi: 10.1073/pnas.94.26.14231.
Our study of the extended metal environment, particularly of the second shell, focuses in this paper on zinc sites. Key findings include: (i) The second shell of mononuclear zinc centers is generally more polar than hydrophobic and prominently features charged residues engaged in an abundance of hydrogen bonding with histidine ligands. Histidine-acidic or histidine-tyrosine clusters commonly overlap the environment of zinc ions. (ii) Histidine tautomeric metal bonding patterns in ligating zinc ions are mixed. For example, carboxypeptidase A, thermolysin, and sonic hedgehog possess the same ligand group (two histidines, one unibidentate acidic ligand, and a bound water), but their histidine tautomeric geometries markedly differ such that the carboxypeptidase A makes only Ndelta1 contacts, thermolysin makes only Nepsilon2 contacts, and sonic hedgehog uses one of each. Thus the presence of a similar ligand cohort does not necessarily imply the same topology or function at the active site. (iii) Two close histidine ligands HXmH, m </= 5, rarely both coordinate a single metal ion in the Ndelta1 tautomeric conformation, presumably to avoid steric conflicts. Mononuclear zinc sites can be classified into six types depending on the ligand composition and geometry. Implications of the results are discussed in terms of divergent and convergent evolution.
我们对扩展金属环境，特别是第二配位层的研究，在本文中聚焦于锌位点。主要发现包括：（i）单核锌中心的第二配位层通常极性强于疏水性，其显著特征是带电残基与组氨酸配体形成大量氢键。组氨酸-酸性或组氨酸-酪氨酸簇通常与锌离子环境重叠。（ii）连接锌离子的组氨酸互变异构体金属键合模式是混合的。例如，羧肽酶A、嗜热菌蛋白酶和音猬因子具有相同的配体基团（两个组氨酸、一个单齿酸性配体和一个结合水），但它们的组氨酸互变异构体几何结构明显不同，以至于羧肽酶A仅形成Nδ1接触，嗜热菌蛋白酶仅形成Nε2接触，而音猬因子两种接触方式都有。因此，相似配体群的存在并不一定意味着活性位点具有相同的拓扑结构或功能。（iii）两个相邻的组氨酸配体HXmH，m≤5，很少以Nδ1互变异构体构象同时配位单个金属离子，大概是为了避免空间冲突。根据配体组成和几何结构，单核锌位点可分为六种类型。从趋异进化和趋同进化的角度讨论了这些结果的意义。
