3h0v: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3h0v]] is a 2 chain structure with 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=3H0V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3H0V FirstGlance]. <br> | <table><tr><td colspan='2'>[[3h0v]] is a 2 chain structure with 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=3H0V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3H0V FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=M2T:5-DEOXY-5-(DIMETHYL-LAMBDA~4~-SULFANYL)ADENOSINE'>M2T</scene>, <scene name='pdbligand=PUT:1,4-DIAMINOBUTANE'>PUT</scene>, <scene name='pdbligand=PYR:PYRUVIC+ACID'>PYR</scene>< | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=M2T:5-DEOXY-5-(DIMETHYL-LAMBDA~4~-SULFANYL)ADENOSINE'>M2T</scene>, <scene name='pdbligand=PUT:1,4-DIAMINOBUTANE'>PUT</scene>, <scene name='pdbligand=PYR:PYRUVIC+ACID'>PYR</scene></td></tr> | ||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1jen|1jen]], [[1i7b|1i7b]], [[1i7c|1i7c]], [[1i7m|1i7m]], [[1i72|1i72]], [[1i79|1i79]], [[3h0w|3h0w]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1jen|1jen]], [[1i7b|1i7b]], [[1i7c|1i7c]], [[1i7m|1i7m]], [[1i72|1i72]], [[1i79|1i79]], [[3h0w|3h0w]]</td></tr> | ||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AMD1, AMD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AMD1, AMD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | ||
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenosylmethionine_decarboxylase Adenosylmethionine decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.50 4.1.1.50] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenosylmethionine_decarboxylase Adenosylmethionine decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.50 4.1.1.50] </span></td></tr> | ||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3h0v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3h0v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3h0v RCSB], [http://www.ebi.ac.uk/pdbsum/3h0v 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=3h0v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3h0v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3h0v RCSB], [http://www.ebi.ac.uk/pdbsum/3h0v PDBsum]</span></td></tr> | ||
<table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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[[Category: Adenosylmethionine decarboxylase]] | [[Category: Adenosylmethionine decarboxylase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Bale, S | [[Category: Bale, S]] | ||
[[Category: Brooks, W H | [[Category: Brooks, W H]] | ||
[[Category: Ealick, S E | [[Category: Ealick, S E]] | ||
[[Category: Guida, W C | [[Category: Guida, W C]] | ||
[[Category: Hanes, J W | [[Category: Hanes, J W]] | ||
[[Category: Mahesan, A M | [[Category: Mahesan, A M]] | ||
[[Category: Adometdc with competitive substrate analog]] | [[Category: Adometdc with competitive substrate analog]] | ||
[[Category: Autocatalytic cleavage]] | [[Category: Autocatalytic cleavage]] | ||
Revision as of 14:03, 20 January 2015
Human AdoMetDC with 5'-Deoxy-5'-(dimethylsulfonio) adenosineHuman AdoMetDC with 5'-Deoxy-5'-(dimethylsulfonio) adenosine
Structural highlights
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 PubMedS-Adenosylmethionine decarboxylase (AdoMetDC) is a key enzyme in the polyamine biosynthetic pathway. Inhibition of this pathway and subsequent depletion of polyamine levels is a viable strategy for cancer chemotherapy and for the treatment of parasitic diseases. Substrate analogue inhibitors display an absolute requirement for a positive charge at the position equivalent to the sulfonium of S-adenosylmethionine. We investigated the ligand specificity of AdoMetDC through crystallography, quantum chemical calculations, and stopped-flow experiments. We determined crystal structures of the enzyme cocrystallized with 5'-deoxy-5'-dimethylthioadenosine and 5'-deoxy-5'-(N-dimethyl)amino-8-methyladenosine. The crystal structures revealed a favorable cation-pi interaction between the ligand and the aromatic side chains of Phe7 and Phe223. The estimated stabilization from this interaction is 4.5 kcal/mol as determined by quantum chemical calculations. Stopped-flow kinetic experiments showed that the rate of the substrate binding to the enzyme greatly depends on Phe7 and Phe223, thus supporting the importance of the cation-pi interaction. Role of the Sulfonium Center in Determining the Ligand Specificity of Human S-Adenosylmethionine Decarboxylase.,Bale S, Brooks W, Hanes JW, Mahesan AM, Guida WC, Ealick SE Biochemistry. 2009 Jun 15. PMID:19527050[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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