S1 Fig. Multiple sequence alignment of IPMK proteins from <i>Plasmodium</i> species that infect humans.

Sequences from P. falciparum (Q8I3W0), P. malariae (A0A1D3RII6), P. vivax (A0A564ZW73), P. ovale (A0A1D3U8P3) and P. knowlesi (B3L6B8) were aligned with Clustal Omega and viewed in Jalview. The sequences in the grey frame highlight the identified signature motifs QxxxDxKxG, SLL and IDF. Invariant residues are shaded blue. S1 Table. List of IPK proteins used for structural analysis and their annotations. S2 Fig. Modelling and structure assessment of P. falciparum IPMK1. (A & C) Local distance difference test (LDDT) score per position predicted for the five P. falciparum IPMK1_kinase domain models generated by Colabfold. The model predictions had high- and low-confidence regions, and the low-confidence areas (red, blue and orange frames) were intrinsically disordered regions. (B) PAE plot of the best model predicted, which was refined and analysed on ProSA-Web (E) and SAVES (D), showing that 94.5% was Ramachandran favoured. S3 Fig. 3D modelling of the PfIPMK kinase domain by SWISS-MODEL. (A) Template information. (B) Model assessment of the predicted P. falciparum IPMK2 domain showing a Ramachandra plot of the initial model structure and that of the refined model, which has 94.4% of its residues in the favoured regions (D). (C) ProSA-web output of the quality assessment of the refined model. S2 Table. Table of druggable pockets predicted by PockDrug for P. falciparum IPMK2 and their parameters. S3 Table. Summary of the predicted subcellular locations of the putative P. falciparum IPKs. S1 Sequence. Predicted amino acid sequence of P. falciparum 3D7 IPMK1. S4 Table. Peptides mapped to enzymes in the P. falciparum IPP. S1 document. Uncropped images. (ZIP)本研究对恶性疟原虫（*Plasmodium falciparum*，UniProt登录号Q8I3W0）、三日疟原虫（*Plasmodium malariae*，A0A1D3RII6）、间日疟原虫（*Plasmodium vivax*，A0A564ZW73）、卵形疟原虫（*Plasmodium ovale*，A0A1D3U8P3）以及诺氏疟原虫（*Plasmodium knowlesi*，B3L6B8）的蛋白序列进行了Clustal Omega多序列比对，并使用Jalview进行可视化展示。灰色框内的序列标注了已鉴定的特征基序QxxxDxKxG、SLL与IDF，保守残基以蓝色高亮显示。 S1表：用于结构分析的肌醇多磷酸激酶（Inositol Polyphosphate Kinases, IPK）蛋白列表及其注释信息。 S2图：恶性疟原虫IPMK1的建模与结构评估。（A与C）Colabfold生成的5个恶性疟原虫IPMK1激酶结构域模型的各位点局部距离差异测试（Local Distance Difference Test, LDDT）得分。该模型预测结果包含高置信度与低置信度区域，其中低置信度区域（红色、蓝色与橙色框）为内在无序区域。（B）最优预测模型的配对误差（Predicted Aligned Error, PAE）图，该模型经ProSA-Web（E）与SAVES（D）优化分析后，结果显示94.5%的残基处于Ramachandran偏好区域。 S3图：采用SWISS-MODEL对恶性疟原虫IPMK激酶结构域进行三维建模。（A）模板信息。（B）对预测的恶性疟原虫IPMK2结构域的模型评估，包含初始模型与优化后模型的Ramachandran构象图，其中优化后模型有94.4%的残基处于偏好区域（D）。（C）优化后模型质量评估的ProSA-Web输出结果。 S2表：PockDrug预测的恶性疟原虫IPMK2可药物结合口袋及其参数列表。 S3表：推定的恶性疟原虫IPKs的预测亚细胞定位汇总。 S1序列：恶性疟原虫3D7株IPMK1的预测氨基酸序列。 S4表：映射到恶性疟原虫IPP相关酶的肽段列表。 S1文档：未裁剪的原始图像文件（ZIP压缩格式）。