3ZU0
Structure of Haemophilus influenzae NAD nucleotidase (NadN)
Summary for 3ZU0
| Entry DOI | 10.2210/pdb3zu0/pdb |
| Related | 3ZTV |
| Descriptor | NAD NUCLEOTIDASE, ZINC ION, PHOSPHATE ION, ... (5 entities in total) |
| Functional Keywords | hydrolase, periplasmic enzyme haemophilus influenzae, cd73 |
| Biological source | HAEMOPHILUS INFLUENZAE |
| Total number of polymer chains | 2 |
| Total formula weight | 128733.21 |
| Authors | Garavaglia, S.,Bruzzone, S.,Cassani, C.,Canella, L.,Allegrone, G.,Sturla, L.,Mannino, E.,Millo, E.,De Flora, A.,Rizzi, M. (deposition date: 2011-07-13, release date: 2011-12-14, Last modification date: 2023-12-20) |
| Primary citation | 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 Cited by 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: 21933152DOI: 10.1042/BJ20111263 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.001 Å) |
Structure validation
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