4IPI

Crystal Structure of R314A N-acetyl Neuraminic Acid Synthase from Neiserria meningitidis with Malate bound

4IPI の概要

• エントリーDOI: 10.2210/pdb4ipi/pdb
• 関連するPDBエントリー: 1XUU 1XUZ 4IPJ
• 分子名称: Polysialic acid capsule biosynthesis protein SiaC, MANGANESE (II) ION, (2S)-2-hydroxybutanedioic acid, ... (4 entities in total)
• 機能のキーワード: antifreeze protein fold, nana, n-acetylneuraminic acid, sialic acid, neisseria meningitidis, transferase
• 由来する生物種: Neisseria meningitidis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38760.85

構造登録者

Joseph, D.D.A.,Jiao, W.,Parker, E.J. (登録日: 2013-01-09, 公開日: 2013-04-10, 最終更新日: 2023-09-20)

主引用文献

Joseph, D.D.,Jiao, W.,Parker, E.J.
Arg314 Is Essential for Catalysis by N-Acetyl Neuraminic Acid Synthase from Neisseria meningitidis.
Biochemistry, 52:2609-2619, 2013

PubMed Abstract: The sialic acid N-acetylneuraminic acid (NANA) has a key role in the pathogenesis of a select number of neuroinvasive bacteria such as Neisseria meningitidis. These pathogens coat themselves with polysialic acids, mimicking the exterior surface of mammalian cells and consequentially concealing the bacteria from the host's immune system. NANA is synthesized in bacteria by the homodimeric enzyme NANA synthase (NANAS), which catalyzes a condensation reaction between phosphoenolpyruvate (PEP) and N-acetylmannosamine (ManNAc). NANAS is closely related to the α-keto acid synthases 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase and 3-deoxy-d-manno-octulosonate 8-phosphate synthase. NANAS differs from these enzymes in that it contains an antifreeze protein like (AFPL) domain, which extends from the C-terminal of the (β/α)8 barrel containing the active site and contributes a highly conserved arginine (Arg314) into the active site of the opposing monomer chain. We have investigated the role of Arg314 in NmeNANAS through mutagenesis and a combination of kinetic and structural analyses. Using isothermal titration calorimetry and molecular modeling, we have shown that Arg314 is required for the catalytic function of NANAS and that the delocalized positively charged guanidinium functionality of this residue provides steering of the sugar substrate ManNAc for suitable placement in the active site and thus reaction with PEP.

PubMed: 23534460
DOI: 10.1021/bi400062c

実験手法

X-RAY DIFFRACTION (1.75 Å)