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| | <StructureSection load='3dz6' size='340' side='right'caption='[[3dz6]], [[Resolution|resolution]] 1.83Å' scene=''> | | <StructureSection load='3dz6' size='340' side='right'caption='[[3dz6]], [[Resolution|resolution]] 1.83Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3dz6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DZ6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DZ6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3dz6]] 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=3DZ6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DZ6 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M8E:5-{[4-(AMINOOXY)BUTYL](METHYL)AMINO}-5-DEOXY-8-ETHENYLADENOSINE'>M8E</scene>, <scene name='pdbligand=PUT:1,4-DIAMINOBUTANE'>PUT</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.83Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PYR:PYRUVIC+ACID'>PYR</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M8E:5-{[4-(AMINOOXY)BUTYL](METHYL)AMINO}-5-DEOXY-8-ETHENYLADENOSINE'>M8E</scene>, <scene name='pdbligand=PUT:1,4-DIAMINOBUTANE'>PUT</scene>, <scene name='pdbligand=PYR:PYRUVIC+ACID'>PYR</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1jen|1jen]], [[1i72|1i72]], [[1i7b|1i7b]], [[1i7c|1i7c]], [[1i7m|1i7m]], [[1i79|1i79]], [[3dz2|3dz2]], [[3dz3|3dz3]], [[3dz4|3dz4]], [[3dz5|3dz5]], [[3dz7|3dz7]]</div></td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AMD1, AMD ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Adenosylmethionine_decarboxylase Adenosylmethionine decarboxylase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.50 4.1.1.50] </span></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=3dz6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dz6 OCA], [https://pdbe.org/3dz6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dz6 RCSB], [https://www.ebi.ac.uk/pdbsum/3dz6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dz6 ProSAT]</span></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=3dz6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dz6 OCA], [https://pdbe.org/3dz6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dz6 RCSB], [https://www.ebi.ac.uk/pdbsum/3dz6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dz6 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/DCAM_HUMAN DCAM_HUMAN] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Adenosylmethionine decarboxylase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bale, S]] | + | [[Category: Bale S]] |
| - | [[Category: Ealick, S E]] | + | [[Category: Ealick SE]] |
| - | [[Category: Guida, W C]] | + | [[Category: Guida WC]] |
| - | [[Category: III, J A.Secrist]]
| + | [[Category: McCloskey DE]] |
| - | [[Category: McCloskey, D E]] | + | [[Category: Pegg AE]] |
| - | [[Category: Pegg, A E]] | + | [[Category: Secrist III JA]] |
| - | [[Category: Complexes of adometdc with 8-substituted ligand]] | + | |
| - | [[Category: Decarboxylase]]
| + | |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: Pyruvate]]
| + | |
| - | [[Category: S-adenosyl-l-methionine]]
| + | |
| - | [[Category: Spermidine biosynthesis]]
| + | |
| - | [[Category: Zymogen]]
| + | |
| Structural highlights
Function
DCAM_HUMAN
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
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ McCloskey DE, Bale S, Secrist JA, Tiwari A, Moss TH, Valiyaveettil J, Brooks WH, Guida WC, Pegg AE, Ealick SE. 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). J Med Chem. 2009 Feb 11. PMID:19209891 doi:10.1021/jm801126a
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