2i6a: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
(10 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:2i6a.jpg|left|200px]]


<!--
==Human Adenosine Kinase in Complex With 5'-Deoxy-5-Iodotubercidin==
The line below this paragraph, containing "STRUCTURE_2i6a", creates the "Structure Box" on the page.
<StructureSection load='2i6a' size='340' side='right'caption='[[2i6a]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)  
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[2i6a]] is a 4 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=2I6A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2I6A FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
-->
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5I5:7-(5-DEOXY-BETA-D-RIBOFURANOSYL)-5-IODO-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE'>5I5</scene></td></tr>
{{STRUCTURE_2i6a| PDB=2i6a |  SCENE= }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2i6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i6a OCA], [https://pdbe.org/2i6a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2i6a RCSB], [https://www.ebi.ac.uk/pdbsum/2i6a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2i6a ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/ADK_HUMAN ADK_HUMAN] Defects in ADK are the cause of hypermethioninemia due to adenosine kinase deficiency (HMAKD) [MIM:[https://omim.org/entry/614300 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.<ref>PMID:21963049</ref>
== Function ==
[https://www.uniprot.org/uniprot/ADK_HUMAN 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.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i6/2i6a_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2i6a ConSurf].
<div style="clear:both"></div>


'''Human Adenosine Kinase in Complex With 5'-Deoxy-5-Iodotubercidin'''
==See Also==
 
*[[Adenosine kinase 3D structures|Adenosine kinase 3D structures]]
 
*[[Adenylate kinase 3D structures|Adenylate kinase 3D structures]]
==Overview==
== References ==
Adenosine kinase (AK) is an enzyme responsible for converting endogenous adenosine (ADO) to adenosine monophosphate (AMP) in an adenosine triphosphate- (ATP-) dependent manner. The structure of AK consists of two domains, the first a large alpha/beta Rossmann-like nucleotide binding domain that forms the ATP binding site, and a smaller mixed alpha/beta domain, which, in combination with the larger domain, forms the ADO binding site and the site of phosphoryl transfer. AK inhibitors have been under investigation as antinociceptive, antiinflammatory, and anticonvulsant as well as antiinfective agents. In this work, we report the structures of AK in complex with two classes of inhibitors: the first, ADO-like, and the second, a novel alkynylpyrimidine series. The two classes of structures, which contain structurally similar substituents, reveal distinct binding modes in which the AK structure accommodates the inhibitor classes by a 30 degrees rotation of the small domain relative to the large domain. This change in binding mode stabilizes an open and a closed intermediate structural state and provide structural insight into the transition required for catalysis. This results in a significant rearrangement of both the protein active site and the orientation of the alkynylpyrimidine ligand when compared to the observed orientation of nucleosidic inhibitors or substrates.
<references/>
 
__TOC__
==About this Structure==
</StructureSection>
2I6A is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I6A OCA].
 
==Reference==
Crystal structures of human adenosine kinase inhibitor complexes reveal two distinct binding modes., Muchmore SW, Smith RA, Stewart AO, Cowart MD, Gomtsyan A, Matulenko MA, Yu H, Severin JM, Bhagwat SS, Lee CH, Kowaluk EA, Jarvis MF, Jakob CL, J Med Chem. 2006 Nov 16;49(23):6726-31. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17154503 17154503]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Muchmore, S W.]]
[[Category: Muchmore SW]]
[[Category: 5'-deoxy-5-iodotubercidin]]
[[Category: Protein-ligand complex]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 07:07:35 2008''

Latest revision as of 12:01, 21 February 2024

Human Adenosine Kinase in Complex With 5'-Deoxy-5-IodotubercidinHuman Adenosine Kinase in Complex With 5'-Deoxy-5-Iodotubercidin

Structural highlights

2i6a is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.2Å
Ligands:
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.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ 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

2i6a, resolution 2.20Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=2i6a&oldid=4061944"