Crystal structure of guanosine 5'-monophosphate synthetase from the thermophilic bacterium Thermus thermophilus HB8.

Acta Crystallographica Section F Pub Date : 2024-10-01 DOI:10.1107/s2053230x2400877x

Naoki Nemoto,Seiki Baba,Gota Kawai,Gen Ichi Sampei

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Abstract

Guanosine 5'-monophosphate (GMP) synthetase (GuaA) catalyzes the last step of GMP synthesis in the purine nucleotide biosynthetic pathway. This enzyme catalyzes a reaction in which xanthine 5'-monophosphate (XMP) is converted to GMP in the presence of Gln and ATP through an adenyl-XMP intermediate. A structure of an XMP-bound form of GuaA from the domain Bacteria has not yet been determined. In this study, the crystal structure of an XMP-bound form of GuaA from the thermophilic bacterium Thermus thermophilus HB8 (TtGuaA) was determined at a resolution of 2.20 Å and that of an apo form of TtGuaA was determined at 2.10 Å resolution. TtGuaA forms a homodimer, and the monomer is composed of three domains, which is a typical structure for GuaA. Disordered regions in the crystal structure were obtained from the AlphaFold2-predicted model structure, and a model with substrates (Gln, XMP and ATP) was constructed for molecular-dynamics (MD) simulations. The structural fluctuations of the TtGuaA dimer as well as the interactions between the active-site residues were analyzed by MD simulations.

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嗜热菌 HB8 的鸟苷酸合成酶晶体结构。

5'- 磷酸鸟苷（GMP）合成酶（GuaA）催化嘌呤核苷酸生物合成途径中 GMP 合成的最后一步。这种酶催化的反应是，在 Gln 和 ATP 的存在下，5'-单磷酸黄嘌呤（XMP）通过腺嘌呤-XMP 中间体转化为 GMP。目前尚未确定该领域细菌中与 XMP 结合的 GuaA 的结构。本研究测定了嗜热菌 Thermus thermophilus HB8（TtGuaA）的 XMP 结合型 GuaA 的晶体结构，分辨率为 2.20 Å，并测定了 TtGuaA 的 apo 型晶体结构，分辨率为 2.10 Å。TtGuaA 形成一个同源二聚体，单体由三个结构域组成，这是 GuaA 的典型结构。晶体结构中的无序区来自 AlphaFold2 预测的模型结构，并构建了一个含有底物（Gln、XMP 和 ATP）的模型用于分子动力学（MD）模拟。通过 MD 模拟分析了 TtGuaA 二聚体的结构波动以及活性位点残基之间的相互作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Acta Crystallographica Section F

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