3ZTV

Structure of Haemophilus influenzae NAD nucleotidase (NadN)

3ZTV の概要

• エントリーDOI: 10.2210/pdb3ztv/pdb
• 関連するPDBエントリー: 3ZU0
• 分子名称: NAD NUCLEOTIDASE, ZINC ION, ADENOSINE, ... (5 entities in total)
• 機能のキーワード: hydrolase, nad pyrophosphatase, nmn nucleotidase, periplasmic enzyme, cd73
• 由来する生物種: HAEMOPHILUS INFLUENZAE
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 64253.23

構造登録者

Garavaglia, S.,Bruzzone, S.,Cassani, C.,Canella, L.,Allegrone, G.,Sturla, L.,Mannino, E.,Millo, E.,De Flora, A.,Rizzi, M. (登録日: 2011-07-12, 公開日: 2011-12-14, 最終更新日: 2023-12-20)

主引用文献

Garavaglia, S.,Bruzzone, S.,Cassani, C.,Canella, L.,Allegrone, G.,Sturla, L.,Mannino, E.,Millo, E.,De Flora, A.,Rizzi, M.
The High-Resolution Crystal Structure of Periplasmic Haemophilus Influenzae Nad Nucleotidase Reveals a Novel Enzymatic Function of Human Cd73 Related to Nad Metabolism.
Biochem.J., 441:131-, 2012

PubMed Abstract: Haemophilus influenzae is a major pathogen of the respiratory tract in humans that has developed the capability to exploit host NAD(P) for its nicotinamide dinucleotide requirement. This strategy is organized around a periplasmic enzyme termed NadN (NAD nucleotidase), which plays a central role by degrading NAD into adenosine and NR (nicotinamide riboside), the latter being subsequently internalized by a specific permease. We performed a biochemical and structural investigation on H. influenzae NadN which determined that the enzyme is a Zn2+-dependent 5'-nucleotidase also endowed with NAD(P) pyrophosphatase activity. A 1.3 Å resolution structural analysis revealed a remarkable conformational change that occurs during catalysis between the open and closed forms of the enzyme. NadN showed a broad substrate specificity, recognizing either mono- or di-nucleotide nicotinamides and different adenosine phosphates with a maximal activity on 5'-adenosine monophosphate. Sequence and structural analysis of H. influenzae NadN led us to discover that human CD73 is capable of processing both NAD and NMN, therefore disclosing a possible novel function of human CD73 in systemic NAD metabolism. Our data may prove to be useful for inhibitor design and disclosed unanticipated fascinating evolutionary relationships.

PubMed: 21933152
DOI: 10.1042/BJ20111263

実験手法

X-RAY DIFFRACTION (1.3 Å)