1ndw: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
New page: left|200px<br /><applet load="1ndw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ndw, resolution 2.0Å" /> '''Crystal Structure of ...
 
No edit summary
 
(14 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:1ndw.gif|left|200px]]<br /><applet load="1ndw" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1ndw, resolution 2.0&Aring;" />
'''Crystal Structure of Adenosine Deaminase Complexed with FR221647'''<br />


==Overview==
==Crystal Structure of Adenosine Deaminase Complexed with FR221647==
We disclose herein the rapid discovery of the first highly potent (Ki = 7.7 nM) non-nucleoside adenosine deaminase (ADA) inhibitor based on the rational hybridization of two structurally distinct leads. Two micromolar inhibitors were discovered by a parallel rational design and random screening program, and individual crystal structures of bovine ADA in complexation with these inhibitors revealed several unknown binding sites and distinct binding modes. Using this information as the starting point, highly effective lead hybridization was achieved in only two structure-based drug design iterations. The conceptual approach illustrated by this example promises to be broadly useful in the search for new chemical entities and can contribute greatly to improve the overall efficiency and speed of drug discovery.
<StructureSection load='1ndw' size='340' side='right'caption='[[1ndw]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1ndw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NDW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NDW 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]] 2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FR2:1-((1R)-1-(HYDROXYMETHYL)-3-PHENYLPROPYL)-1H-IMIDAZOLE-4-CARBOXAMIDE'>FR2</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=1ndw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ndw OCA], [https://pdbe.org/1ndw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ndw RCSB], [https://www.ebi.ac.uk/pdbsum/1ndw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ndw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ADA_BOVIN ADA_BOVIN] Catalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine. Plays an important role in purine metabolism and in adenosine homeostasis. Modulates signaling by extracellular adenosine, and so contributes indirectly to cellular signaling events. Acts as a positive regulator of T-cell coactivation, by binding DPP4. Its interaction with DPP4 regulates lymphocyte-epithelial cell adhesion (By similarity).
== 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/nd/1ndw_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=1ndw ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1NDW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with ZN and FR2 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Adenosine_deaminase Adenosine deaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.4 3.5.4.4] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1NDW OCA].
*[[Adenosine deaminase 3D structures|Adenosine deaminase 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
A highly potent non-nucleoside adenosine deaminase inhibitor: efficient drug discovery by intentional lead hybridization., Terasaka T, Kinoshita T, Kuno M, Nakanishi I, J Am Chem Soc. 2004 Jan 14;126(1):34-5. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14709046 14709046]
[[Category: Adenosine deaminase]]
[[Category: Bos taurus]]
[[Category: Bos taurus]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Kinoshita, T.]]
[[Category: Kinoshita T]]
[[Category: FR2]]
[[Category: ZN]]
[[Category: sbdd]]
[[Category: tim-barrel]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 22:10:27 2007''

Latest revision as of 16:27, 13 March 2024

Crystal Structure of Adenosine Deaminase Complexed with FR221647Crystal Structure of Adenosine Deaminase Complexed with FR221647

Structural highlights

1ndw is a 1 chain structure with sequence from Bos taurus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ADA_BOVIN Catalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine. Plays an important role in purine metabolism and in adenosine homeostasis. Modulates signaling by extracellular adenosine, and so contributes indirectly to cellular signaling events. Acts as a positive regulator of T-cell coactivation, by binding DPP4. Its interaction with DPP4 regulates lymphocyte-epithelial cell adhesion (By similarity).

Evolutionary Conservation

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

See Also

1ndw, resolution 2.00Å

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=1ndw&oldid=4087526"