Candida albicans is a widespread human pathogen which can infect humans at different levels. Like the majority of microorganisms, it needs transition metals as micronutrients for its subsistence. In order to acquire these nutrients from the host, C. albicans employs various strategies, also involving chelating proteins specifically expressed to sequester metals from the environment. A histidine-rich protein sequence identified in the C. albicans genome, named C4YJH2, has been recently studied for its putative role in Zn(II) transport. Two outer membrane major histidine-rich clusters of C4YJH2, namely the domains 131–148 (FHEHGHSHSHGSGGGGGG) and 157–165 (SHSHSHSHS), have been confirmed as strong binding sites for the Cu(II) and Zn(II) ions. Nevertheless, the 9-residue “linker” sequence 148–156 (GSDHSGDSK) between the two His-rich fragments of C4YJH2, containing an additional His residue, can also contribute to metal binding. In the present work, the protected peptide Ac-GSDHSGDSK-NH₂ and some analogues (Ac-GSDHSGASK-NH₂, Ac-GADHAGDAK-NH₂, Ac-GSDH-NH₂, and Ac-HSGD-NH₂) have been synthesized and their metal binding properties have been studied in detail. The thermodynamics of complex-formation equilibria of the above reported ligands with Cu(II) and Zn(II) ions have been studied by potentiometry in a wide pH range and the stoichiometry of the formed species has been confirmed by mass spectrometry; the most likely solution structures of the metal complexes are also discussed on the basis of NMR, UV-vis, circular dichroism (CD) and EPR data. The results show the importance of Asp7 in the stabilization of Zn(II) complexes and suggest a significant role of the (quite abundant) Ser residues in the task of metal uptake and regulation.

中文翻译：

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Cu（ii）和Zn（ii）与C4YJH2（148-156）肽片段的复合物的热力学和光谱研究，C4YJH2是白色念珠菌的推定金属转运蛋白。

白色念珠菌是一种广泛的人类病原体，可以以不同水平感染人类。像大多数微生物一样，它需要过渡金属作为其生存所需的微量营养素。为了从宿主获得这些营养素，白色念珠菌采用了多种策略，还涉及螯合专门表达以隔离环境中金属的蛋白质。最近已研究了在白色念珠菌基因组中鉴定出的富含组氨酸的蛋白质序列C4YJH2，因为它在Zn（II）转运中具有推定作用。C4YJH2的两个富含外膜的主要组氨酸富集簇，即域131–148（FHEHGHSHSHGSGGGGGGGG）和157–165（SHSHSHSHS），已被证实是Cu（II）和Zn（II）离子。但是，两个富含His的C4YJH2富含His的片段之间的9个残基的“连接子”序列148-156（GSDHSGDSK）也可以促进金属结合。在本工作中，已合成了保护肽Ac-GSDHSGDSK-NH ₂和一些类似物（Ac-GSDHSGASK-NH ₂，Ac-GADHAGDAK-NH ₂，Ac-GSDH-NH ₂和Ac-HSGD-NH ₂）。并且已经详细研究了它们的金属结合性能。上述报道的配体与Cu（II）和Zn（II）的络合物形成平衡的热力学）已在较宽的pH范围内通过电位法研究了离子，并已通过质谱法确定了所形成物质的化学计量；还根据NMR，UV-vis，圆二色性（CD）和EPR数据讨论了金属络合物最可能的溶液结构。结果表明Asp7在稳定Zn（II）配合物中的重要性，并表明（相当丰富的）Ser残基在金属吸收和调节中起着重要作用。