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首页> 外文期刊>Biochemistry >Differential ligand recognition by the SRC and phosphatidylinositol 3-kinase SRC homology 3 domains: circular dichroism and ultraviolet resonance Raman studies.
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Differential ligand recognition by the SRC and phosphatidylinositol 3-kinase SRC homology 3 domains: circular dichroism and ultraviolet resonance Raman studies.

机译：SRC和磷脂酰肌醇的差分配体识别3-激酶SRC同源3结构域：圆形二色性和紫外共振拉曼研究。

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摘要

Src homology 3 (SH3) domains recognize Pro-rich motifs using a hydrophobic cleft which contains several conserved aromatic residues. To investigate how aromatic residues contribute to ligand recognition, circular dichroism (CD) and 235 nm excited ultraviolet resonance Raman spectroscopies have been applied to Src and phosphatidylinositol 3-kinase (PI3K) SH3s. The CD analysis shows that Src SH3 binds to RPLPPLP (R-core) using aromatic residues with a dissociation constant (K(d)) of 10 microM. Moreover, intensity increases of the Trp and Tyr Raman bands suggest that the interaction is mediated by hydrophobic contacts and/or hydrogen bond formation with both Trp and Tyr residues. In the interaction of Src SH3 with VSLARRPLPPLP (VSL12) (K(d) 0.8 microM), Trp118 appears to form a strong hydrogen bond with VSL12, judging from significant intensity increases of the Trp Raman bands and the reported complex structure. In contrast, PI3K SH3 binds to R-core and VSL12 with lower affinities (K(d) 34 and 18 microM, respectively), and the interactions are suggested to be mediated mainly by hydrophobic contacts and/or hydrogen bond formation with Tyr residue(s). In the D21N mutant (Asp21 --> Asn) of PI3K SH3, whose hydrophobic cleft is deformed, Trp55 is shown to be responsible for the interaction with VSL12 by intensity increases of the Trp Raman bands. However, the affinity is severely decreased (K(d) 330 microM). These observations imply that SH3 domains associate with their ligands with distinct use of aromatic residues and that hydrogen bond formation with an SH3-conserved Trp residue in the well-ordered hydrophobic cleft is important for stable complex formation.
机译：SRC同源性3（SH3）结构域使用疏水性裂隙识别富含富含型芳香族残留物的富含族裂缝。为了研究芳族残基如何有助于配体识别，圆形二色性（CD）和235nm激发紫外共振拉曼光谱已经应用于SRC和磷脂酰肌醇3-激酶（PI3K）SH3。 CD分析表明，SRC SH3使用具有10μm的解离常数（K（d））的芳族残基与RPLPPLP（R核）结合。此外，TRP和Tyr拉曼带的强度增加表明，相互作用是通过疏水触点和/或氢键形成介导的TRP和Tyr残基。在SRC SH3与VSLARRPLPPLP（VSL12）的相互作用中（k（d）0.8 microm），TRP118似乎与VSL12形成强氢键，从TRP拉曼带的显着强度增加和报告的复杂结构判断。相反，PI3K SH3与R-Core和VSL12结合，具有较低亲和力（分别为k（d）34和18微米），并建议将相互作用主要通过疏水触点和/或用Tyr残基形成介导的相互作用（ s）。在PI3K SH3的D21N突变体（ASP21-> ASN）中，其疏水性裂缝变形，TRP55被示出为通过TRP拉曼带的强度增加与VSL12的相互作用。然而，亲和力严重降低（K（d）330微米）。这些观察结果暗示SH3结构域与它们的配体具有不同用途的芳族残基，并且在有序疏水性裂缝中具有SH3保守的TRP残基的氢键形成对于稳定的复合物形成是重要的。

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