2e1w

From Proteopedia

(Difference between revisions)

Revision as of 06:41, 6 June 2018

Crystal structure of adenosine deaminase complexed with potent inhibitors

Structural highlights

2e1w is a 1 chain structure with sequence from Bos taurus. This structure supersedes the now removed PDB entry 1v78. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1v79, 1v7a
Activity:	Adenosine deaminase, with EC number 3.5.4.4
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.

Publication Abstract from PubMed

We disclose optimization efforts based on the novel non-nucleoside adenosine deaminase (ADA) inhibitor, 4 (K(i) = 680 nM). Structure-based drug design utilizing the crystal structure of the 4/ADA complex led to discovery of 5 (K(i) = 11 nM, BA = 30% in rats). Furthermore, from metabolic considerations, we discovered two inhibitors with improved oral bioavailability [6 (K(i) = 13 nM, BA = 44%) and 7 (K(i) = 9.8 nM, BA = 42%)]. 6 demonstrated in vivo efficacy in models of inflammation and lymphoma.

Structure-based design and synthesis of non-nucleoside, potent, and orally bioavailable adenosine deaminase inhibitors.,Terasaka T, Okumura H, Tsuji K, Kato T, Nakanishi I, Kinoshita T, Kato Y, Kuno M, Seki N, Naoe Y, Inoue T, Tanaka K, Nakamura K J Med Chem. 2004 May 20;47(11):2728-31. PMID:15139750^[1]

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

References

↑ Terasaka T, Okumura H, Tsuji K, Kato T, Nakanishi I, Kinoshita T, Kato Y, Kuno M, Seki N, Naoe Y, Inoue T, Tanaka K, Nakamura K. Structure-based design and synthesis of non-nucleoside, potent, and orally bioavailable adenosine deaminase inhibitors. J Med Chem. 2004 May 20;47(11):2728-31. PMID:15139750 doi:http://dx.doi.org/10.1021/jm0499559

1 Structural highlights
2 Function
3 Evolutionary Conservation
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/2e1w"

@@ Line 1: / Line 1: @@
 ==Crystal structure of adenosine deaminase complexed with potent inhibitors==
 <StructureSection load='2e1w' size='340' side='right' caption='[[2e1w]], [[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">[[1v79|1v79]], [[1v7a|1v7a]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </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=2e1w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e1w OCA], [http://pdbe.org/2e1w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2e1w RCSB], [http://www.ebi.ac.uk/pdbsum/2e1w 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=2e1w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e1w OCA], [http://pdbe.org/2e1w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2e1w RCSB], [http://www.ebi.ac.uk/pdbsum/2e1w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2e1w ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e1/2e1w_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e1/2e1w_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 41: / Line 42: @@
 [[Category: Beta barrel]]
 [[Category: Hydrolase]]
+[[Category: Zinc]]

2e1w

From Proteopedia

Revision as of 06:41, 6 June 2018

Crystal structure of adenosine deaminase complexed with potent inhibitors

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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