4o1l

From Proteopedia

(Difference between revisions)

Revision as of 10:45, 11 August 2016

Human Adenosine Kinase in complex with inhibitor

Structural highlights

4o1l is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	4pvv
Activity:	Adenosine kinase, with EC number 2.7.1.20
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[ADK_HUMAN] Defects in ADK are the cause of hypermethioninemia due to adenosine kinase deficiency (HMAKD) [MIM:614300]. A metabolic disorder characterized by global developmental delay, early-onset seizures, mild dysmorphic features, and characteristic biochemical anomalies, including persistent hypermethioninemia with increased levels of S-adenosylmethionine and S-adenosylhomocysteine. Homocysteine levels are typically normal.^[1]

Function

[ADK_HUMAN] ATP dependent phosphorylation of adenosine and other related nucleoside analogs to monophosphate derivatives. Serves as a potential regulator of concentrations of extracellular adenosine and intracellular adenine nucleotides.

Publication Abstract from PubMed

Adenosine kinase (ADK) from Mycobacterium tuberculosis (Mtb) was selected as a target for design of antimycobacterial nucleosides. Screening of 7-(het)aryl-7-deazaadenine ribonucleosides with Mtb and human (h) ADKs and testing with wild-type and drug-resistant Mtb strains identified specific inhibitors of Mtb ADK with micromolar antimycobacterial activity and low cytotoxicity. X-ray structures of complexes of Mtb and hADKs with 7-ethynyl-7-deazaadenosine showed differences in inhibitor interactions in the adenosine binding sites. 1D (1)H STD NMR experiments revealed that these inhibitors are readily accommodated into the ATP and adenosine binding sites of Mtb ADK, whereas they bind preferentially into the adenosine site of hADK. Occupation of the Mtb ADK ATP site with inhibitors and formation of catalytically less competent semiopen conformation of MtbADK after inhibitor binding in the adenosine site explain the lack of phosphorylation of 7-substituted-7-deazaadenosines. Semiempirical quantum mechanical analysis confirmed different affinity of nucleosides for the Mtb ADK adenosine and ATP sites.

Structural Basis for Inhibition of Mycobacterial and Human Adenosine Kinase by 7-Substituted 7-(Het)aryl-7-deazaadenine Ribonucleosides.,Snasel J, Naus P, Dostal J, Hnizda A, Fanfrlik J, Brynda J, Bourderioux A, Dusek M, Dvorakova H, Stolarikova J, Zabranska H, Pohl R, Konecny P, Dzubak P, Votruba I, Hajduch M, Rezacova P, Veverka V, Hocek M, Pichova I J Med Chem. 2014 Oct 23;57(20):8268-79. doi: 10.1021/jm500497v. Epub 2014 Oct 8. PMID:25259627^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bjursell MK, Blom HJ, Cayuela JA, Engvall ML, Lesko N, Balasubramaniam S, Brandberg G, Halldin M, Falkenberg M, Jakobs C, Smith D, Struys E, von Dobeln U, Gustafsson CM, Lundeberg J, Wedell A. Adenosine kinase deficiency disrupts the methionine cycle and causes hypermethioninemia, encephalopathy, and abnormal liver function. Am J Hum Genet. 2011 Oct 7;89(4):507-15. doi: 10.1016/j.ajhg.2011.09.004. Epub, 2011 Sep 28. PMID:21963049 doi:10.1016/j.ajhg.2011.09.004
↑ Snasel J, Naus P, Dostal J, Hnizda A, Fanfrlik J, Brynda J, Bourderioux A, Dusek M, Dvorakova H, Stolarikova J, Zabranska H, Pohl R, Konecny P, Dzubak P, Votruba I, Hajduch M, Rezacova P, Veverka V, Hocek M, Pichova I. Structural Basis for Inhibition of Mycobacterial and Human Adenosine Kinase by 7-Substituted 7-(Het)aryl-7-deazaadenine Ribonucleosides. J Med Chem. 2014 Oct 23;57(20):8268-79. doi: 10.1021/jm500497v. Epub 2014 Oct 8. PMID:25259627 doi:http://dx.doi.org/10.1021/jm500497v

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4o1l"

@@ Line 1: / Line 1: @@
 ==Human Adenosine Kinase in complex with inhibitor==
 <StructureSection load='4o1l' size='340' side='right' caption='[[4o1l]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4pvv|4pvv]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenosine_kinase Adenosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.20 2.7.1.20] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4o1l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o1l OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4o1l RCSB], [http://www.ebi.ac.uk/pdbsum/4o1l PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4o1l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o1l OCA], [http://pdbe.org/4o1l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4o1l RCSB], [http://www.ebi.ac.uk/pdbsum/4o1l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4o1l ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 20: / Line 21: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4o1l" style="background-color:#fffaf0;"></div>
 ==See Also==

4o1l

From Proteopedia

Revision as of 10:45, 11 August 2016

Human Adenosine Kinase in complex with inhibitor

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

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