Structural highlights
4h2f is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
|
| Ligands: | , , , |
| Related: | 4h2g, 4h2i, 4h1y, 4h2b |
| Gene: | NT5E, NT5, NTE (HUMAN) |
| Activity: | 5'-nucleotidase, with EC number 3.1.3.5 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[5NTD_HUMAN] Hereditary arterial and articular multiple calcification syndrome. The disease is caused by mutations affecting the gene represented in this entry.
Function
[5NTD_HUMAN] Hydrolyzes extracellular nucleotides into membrane permeable nucleosides. Exhibits AMP-, NAD-, and NMN-nucleosidase activities.[1]
Publication Abstract from PubMed
In vertebrates ecto-5'-nucleotidase (e5NT) catalyzes the hydrolysis of extracellular AMP to adenosine and represents the major control point for extracellular adenosine levels. Due to its pivotal role for activation of P1 adenosine receptors, e5NT has emerged as an appealing drug target for treatment of inflammation, chronic pain, hypoxia, and cancer. Crystal structures of the dimeric human e5NT reveal an extensive 114 degrees conformational switch between the open and closed forms of the enzyme. The dimerization interface is formed by the C-terminal domains and exhibits interchain motions of up to 13 degrees . Complex structures with adenosine and AMPCP indicate that structural control of the domain movement determines the selectivity for monophosphate nucleotides. Binding modes of nucleotide-derived and flavonoid-based compounds complexed to the C-terminal domain in the open form reveal an additional binding pocket of approximately 210 A(3) that might be explored to design more potent inhibitors.
Crystal Structure of the Human Ecto-5'-Nucleotidase (CD73): Insights into the Regulation of Purinergic Signaling.,Knapp K, Zebisch M, Pippel J, El-Tayeb A, Muller CE, Strater N Structure. 2012 Nov 6. pii: S0969-2126(12)00375-9. doi:, 10.1016/j.str.2012.10.001. PMID:23142347[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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. 2011 Sep 20. PMID:21933152 doi:10.1042/BJ20111263
- ↑ Knapp K, Zebisch M, Pippel J, El-Tayeb A, Muller CE, Strater N. Crystal Structure of the Human Ecto-5'-Nucleotidase (CD73): Insights into the Regulation of Purinergic Signaling. Structure. 2012 Nov 6. pii: S0969-2126(12)00375-9. doi:, 10.1016/j.str.2012.10.001. PMID:23142347 doi:http://dx.doi.org/10.1016/j.str.2012.10.001
