4h2b: Difference between revisions
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==Human ecto-5'-nucleotidase (CD73): crystal form II (open) in complex with Baicalin== | |||
<StructureSection load='4h2b' size='340' side='right'caption='[[4h2b]], [[Resolution|resolution]] 1.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4h2b]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4H2B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4H2B FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0XE:5,6-DIHYDROXY-4-OXO-2-PHENYL-4H-CHROMEN-7-YL+BETA-D-GLUCOPYRANOSIDURONIC+ACID'>0XE</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4h2b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h2b OCA], [https://pdbe.org/4h2b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4h2b RCSB], [https://www.ebi.ac.uk/pdbsum/4h2b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4h2b ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/5NTD_HUMAN 5NTD_HUMAN] Hereditary arterial and articular multiple calcification syndrome. The disease is caused by mutations affecting the gene represented in this entry. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/5NTD_HUMAN 5NTD_HUMAN] Hydrolyzes extracellular nucleotides into membrane permeable nucleosides. Exhibits AMP-, NAD-, and NMN-nucleosidase activities.<ref>PMID:21933152</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:23142347</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== | <div class="pdbe-citations 4h2b" style="background-color:#fffaf0;"></div> | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Knapp | [[Category: Large Structures]] | ||
[[Category: Pippel | [[Category: Knapp K]] | ||
[[Category: Straeter | [[Category: Pippel J]] | ||
[[Category: Zebisch | [[Category: Straeter N]] | ||
[[Category: Zebisch M]] | |||
Latest revision as of 13:54, 6 November 2024
Human ecto-5'-nucleotidase (CD73): crystal form II (open) in complex with BaicalinHuman ecto-5'-nucleotidase (CD73): crystal form II (open) in complex with Baicalin
Structural highlights
Disease5NTD_HUMAN Hereditary arterial and articular multiple calcification syndrome. The disease is caused by mutations affecting the gene represented in this entry. Function5NTD_HUMAN Hydrolyzes extracellular nucleotides into membrane permeable nucleosides. Exhibits AMP-, NAD-, and NMN-nucleosidase activities.[1] Publication Abstract from PubMedIn 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
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