BINDING TO PROTEIN TARGETS OF PEPTIDIC LEADS DISCOVERED BY PHAGE DISPLAY - CRYSTAL-STRUCTURES OF STREPTAVIDIN-BOUND LINEAR AND CYCLIC PEPTIDE LIGANDS CONTAINING THE HPQ SEQUENCE
BINDING TO PROTEIN TARGETS OF PEPTIDIC LEADS DISCOVERED BY PHAGE DISPLAY - CRYSTAL-STRUCTURES OF STREPTAVIDIN-BOUND LINEAR AND CYCLIC PEPTIDE LIGANDS CONTAINING THE HPQ SEQUENCE
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DOI：
10.1021/bi00047a005
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发表时间：
1995-11-28
期刊：
影响因子：
2.9
通讯作者：
KATZ, BA
中科院分区：
文献类型：
--
作者：
KATZ, BA
测定了两种二硫键桥联的环状肽（环-Ac-[CHPQGPPC]-NH 2和环-Ac-[CHPQFC]-NH 2）和线性肽（FSHPQNT）的链霉亲和素结合的晶体结构，以及脱蛋白链霉亲和素（硫酸链霉亲和素）的结构。研究的线性和二硫键桥接的环肽都具有共同的HPQ构象，并与链霉亲和素发生共同的相互作用，尽管复合物之间的侧翼残基在结构和相互作用上存在显着差异。发现链霉抗生物素蛋白-FSHPQNT晶体结构中的线性肽的构象与公开的相同复合物中的构象不同[Weber，P.C.，Pantoliano，M. W.，& Thompson，L. D.（1992）Biochemistry 31，9350-9354]。在本研究中，配体的HPQNT部分是明确定义的，具有定义Phe的一定密度，而在Weber等人的研究中，仅可以解释结合肽的HPQ片段。两种结合的环肽均采用β-转角，其涉及His主链羰基和i+3残基的主链酰胺NH之间的H-键。在链霉亲和素结合的环-Ac-[CHPQFC]-NH 2结构中，在主链His羰基和主链C-末端Cys酰胺NH基团之间存在额外的H-键，指示α-螺旋。环状肽和线性肽的结合相互作用包括直接氢键、由紧密结合的水分子介导的氢键和疏水相互作用。在基于结构的配体设计的背景下，将上述结构与文献中的链霉亲和素-生物素的结构进行比较和讨论。
The streptavidin-bound crystal structures of two disulfide-bridged cyclic peptides (cyclo-Ac-[CHPQGPPC]-NH2 and cyclo-Ac-[CHPQFC]-NH2) and of a linear peptide (FSHPQNT) were determined, as well as the structure of apostreptavidin (streptavidin-sulfate). Both the linear and disulfide-bridged cyclic peptides studied share a common HPQ conformation and make common interactions with streptavidin, although significant differences in structures and interactions occur for flanking residues among the complexes. The conformation of the linear peptide in the crystal structure of streptavidin-FSHPQNT was found to differ from that in the same complex published [Weber, P. C., Pantoliano, M. W., & Thompson, L. D. (1992) Biochemistry 31, 9350-9354]. In the present investigation, the HPQNT portion of the ligand is well-defined with some density defining the Phe, whereas in the investigation of Weber et al. only the HPQ segment of the bound peptide could be interpreted. Both bound cyclic peptides adopt a beta-turn involving an H-bond between the His main chain carbonyl and the main chain amide NH of the i+3 residue. In the streptavidin-bound cyclo-Ac-[CHPQFC]-NH2 structure, there is an additional H-bond, indicative of alpha-helix, between the main chain His carbonyl and the main chain C-terminal Cys amide NH group. Binding interactions for both cyclic and linear peptides include direct H-bonds, H-bonds mediated by tightly bound water molecules, and hydrophobic interactions. The above structures and that of streptavidin-biotin in the literature are compared and discussed in the context of structure-based ligand design.