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< | ==Human AdoMetDC with 5'-[(3-aminopropyl)methylamino]-5'deoxy-8-methyladenosine== | ||
<StructureSection load='3dz2' size='340' side='right'caption='[[3dz2]], [[Resolution|resolution]] 1.86Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3dz2]] is a 2 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=3DZ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DZ2 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]] 1.86Å</td></tr> | |||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A8M:5-[(3-AMINOPROPYL)(METHYL)AMINO]-5-DEOXY-8-METHYLADENOSINE'>A8M</scene>, <scene name='pdbligand=PUT:1,4-DIAMINOBUTANE'>PUT</scene>, <scene name='pdbligand=PYR:PYRUVIC+ACID'>PYR</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=3dz2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dz2 OCA], [https://pdbe.org/3dz2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dz2 RCSB], [https://www.ebi.ac.uk/pdbsum/3dz2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dz2 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/DCAM_HUMAN DCAM_HUMAN] | |||
== 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/dz/3dz2_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=3dz2 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
S-Adenosylmethionine decarboxylase (AdoMetDC) is a critical enzyme in the polyamine biosynthetic pathway and depends on a pyruvoyl group for the decarboxylation process. The crystal structures of the enzyme with various inhibitors at the active site have shown that the adenine base of the ligands adopts an unusual syn conformation when bound to the enzyme. To determine whether compounds that favor the syn conformation in solution would be more potent AdoMetDC inhibitors, several series of AdoMet substrate analogues with a variety of substituents at the 8-position of adenine were synthesized and analyzed for their ability to inhibit hAdoMetDC. The biochemical analysis indicated that an 8-methyl substituent resulted in more potent inhibitors, yet most other 8-substitutions provided no benefit over the parent compound. To understand these results, we used computational modeling and X-ray crystallography to study C(8)-substituted adenine analogues bound in the active site. | |||
New Insights into the Design of Inhibitors of Human S-Adenosylmethionine Decarboxylase: Studies of Adenine C(8) Substitution in Structural Analogues of S-Adenosylmethionine (dagger).,McCloskey DE, Bale S, Secrist JA, Tiwari A, Moss TH, Valiyaveettil J, Brooks WH, Guida WC, Pegg AE, Ealick SE J Med Chem. 2009 Feb 11. PMID:19209891<ref>PMID:19209891</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3dz2" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[SAM decarboxylase|SAM decarboxylase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Bale S]] | ||
[[Category: | [[Category: Ealick SE]] | ||
[[Category: | [[Category: Guida WC]] | ||
[[Category: McCloskey | [[Category: McCloskey DE]] | ||
[[Category: Pegg | [[Category: Pegg AE]] | ||
[[Category: | [[Category: Secrist III JA]] | ||
Latest revision as of 04:44, 21 November 2024
Human AdoMetDC with 5'-[(3-aminopropyl)methylamino]-5'deoxy-8-methyladenosineHuman AdoMetDC with 5'-[(3-aminopropyl)methylamino]-5'deoxy-8-methyladenosine
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedS-Adenosylmethionine decarboxylase (AdoMetDC) is a critical enzyme in the polyamine biosynthetic pathway and depends on a pyruvoyl group for the decarboxylation process. The crystal structures of the enzyme with various inhibitors at the active site have shown that the adenine base of the ligands adopts an unusual syn conformation when bound to the enzyme. To determine whether compounds that favor the syn conformation in solution would be more potent AdoMetDC inhibitors, several series of AdoMet substrate analogues with a variety of substituents at the 8-position of adenine were synthesized and analyzed for their ability to inhibit hAdoMetDC. The biochemical analysis indicated that an 8-methyl substituent resulted in more potent inhibitors, yet most other 8-substitutions provided no benefit over the parent compound. To understand these results, we used computational modeling and X-ray crystallography to study C(8)-substituted adenine analogues bound in the active site. New Insights into the Design of Inhibitors of Human S-Adenosylmethionine Decarboxylase: Studies of Adenine C(8) Substitution in Structural Analogues of S-Adenosylmethionine (dagger).,McCloskey DE, Bale S, Secrist JA, Tiwari A, Moss TH, Valiyaveettil J, Brooks WH, Guida WC, Pegg AE, Ealick SE J Med Chem. 2009 Feb 11. PMID:19209891[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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