Mechanistic investigation for neutralization of toxic heme by histidine rich protein (HRP2) of malaria parasite using a series of HRP2 model peptides

使用一系列 HRP2 模型肽研究疟原虫富含组氨酸的蛋白 (HRP2) 中和有毒血红素的机制

• 批准号: 15550146
• 负责人: TAJIMA Kunihiko
• 金额: $ 2.43万
• 依托单位: Kyoto Institute of Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15550146/
• 关键词: Malaria; heme; HRP2; heme-HRP2 complex; ESR; coordination; マラリア; ヘム; HRP2タンパク; モデルペプチド; ESR(電子スピン共鳴); マラリアの成長阻害; ヘム代謝; ペプチド; ヘム-ペプチド複合体

A series of model peptides, 9 to 27-mer, of Plasmodium Falciparum histidine rich protein 2(HRP2). The coordination reactions occurring between these peptides and ferric iron complex of meso-porphyrin (Fe(III)MP) were studied by using optical absorption measurements and electron spin resonance spectroscopy at 4.2 K. Based on the optical spectrometric titration, the dissociation constants for the heme-peptide complexes were evaluated. The longest peptide 27-R (three repeat of reciprocal sequence of HRP2 ; Ala-His-His-Ala-His-His-Ala-Ala-Asp), Ala-His-His-Ala-His-His-Ala-Ala-Asp-His-His-Ala-His-His-Ala-His-His-Ala-Ala-Asp-Ala-His-His-Ala-His-His-Ala-Ala-Asp, showed significantly high Kd value as 0.97 μM, which correspond to that of naturally occurring HRP2 (0.77 μM). The Kd values of the peptides revealed concomitant decrease with decrease of the number of His residue, for example, the Kd value of the shortest prptide 10R (Ala-His-His-Ala-Ala-Asp-Ala-His-His-Ala) was evaluated to be 77 mM. The both 27R- and 10R-Fe(III)MP complexes gave an identical absorption maxima (405, 533, and 564 nm) ascribed to be the six coordinate iron porphyrin complex. Taking into account the results of ESR spectroscopy, the both axial ligands of these complexes were identified to be nitrogen atoms of imidazole moiety of His.

恶性疟原虫富组氨酸蛋白2（HRP 2）的一系列模型肽，9 - 27-mer。在4.2K下，用光学吸收光谱和电子自旋共振（ESR）研究了这些多肽与meso-卟啉铁配合物（Fe（III）MP）的配位反应。基于光谱滴定法，测定了血红素-肽复合物的离解常数。最长的肽27-R（HRP 2的相互序列的三个重复序列; Ala-His-His-Ala-His-His-Ala-Ala-Asp），Ala-His-His-Ala-His-Ala-His-Ala-Ala-His-His-Ala-Ala-Asp-Ala-His-His-Ala-His-His-Ala-Ala-Asp显示出显著高的Kd值，为0.97 μM，与天然存在的HRP 2（0.77 μM）相对应。随着His残基数目的减少，肽的Kd值也随之降低，例如，最短肽10 R的Kd值（Ala-His-His-Ala-Ala-Asp-Ala-His-His-Ala）的最大吸收峰为77 mM。27 R-和10 R-Fe（III）MP络合物的最大吸收峰相同（405、533和564 nm）的光致发光，归属于六配位铁卟啉配合物。结合ESR谱的结果，确定了配合物的两个轴向配体均为组氨酸咪唑部分的氮原子。

项目成果

Solution structure of marinostatin, a natural ester-linked protein protease inhibitor

• DOI: 10.1021/bi048034x
• 发表时间: 2005-02-22
• 期刊: BIOCHEMISTRY
• 影响因子: 2.9
• 作者: Kanaori, K;Kamei, K;Hara, S
• 通讯作者: Hara, S

Tajima, M.: "Nitration of 2'-deoxyguanosine by a NO/O2 gas mixture : identification and characterization of N2-nitro-2'-deoxyguanosine"Org.Lett.. 5. 3173-3176 (2003)

Tajima, M.：“NO/O2 气体混合物对 2-脱氧鸟苷的硝化：N2-硝基-2-脱氧鸟苷的鉴定和表征”Org.Lett.. 5. 3173-3176 (2003)

Tajima, K.: "Cu(II) and Zn(II) bound in the triple stranded α-helical coiled-coil activate water molecule : prototype for metalloenzyme"Peptide Synthesis. 1004(In press).

Tajima, K.：“Cu(II) 和 Zn(II) 结合在三链 α-螺旋卷曲螺旋活化水分子中：金属酶的原型”肽合成 1004（出版中）。

Effect of phosphorothioate chirality on i-motif structure and stability.

• DOI: 10.1021/bi035419r
• 发表时间: 2004-05
• 期刊: Biochemistry
• 影响因子: 2.9
• 作者: K. Kanaori;S. Sakamoto;H. Yoshida;P. Guga;W. Stec;K. Tajima;K. Makino

Two-metal ion, Ni(II) and Cu(II), binding α-helix coiled coil peptide

双金属离子 Ni(II) 和 Cu(II)，结合 α-螺旋卷曲肽

• 发表时间: 2004
• 期刊: J.Am.Chem.Soc 126
• 作者: A.Yoshizawa;^* S.Segawa;F.Ogasawara;K.Tajima 他;A.Yoshizawa;K.Tajima 他
• 通讯作者: K.Tajima 他