1i79: Difference between revisions
No edit summary |
No edit summary |
||
| (13 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
< | ==HUMAN S-ADENOSYLMETHIONINE DECARBOXYLASE WITH COVALENTLY BOUND PYRUVOYL GROUP AND COVALENTLY BOUND 5'-DEOXY-5'-[(3-HYDRAZINOPROPYL)METHYLAMINO]ADENOSINE== | ||
<StructureSection load='1i79' size='340' side='right'caption='[[1i79]], [[Resolution|resolution]] 2.01Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1i79]] 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=1I79 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1I79 FirstGlance]. <br> | |||
or | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.01Å</td></tr> | ||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MHZ:5-DEOXY-5-[(3-HYDRAZINOPROPYL)METHYLAMINO]ADENOSINE'>MHZ</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=1i79 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i79 OCA], [https://pdbe.org/1i79 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1i79 RCSB], [https://www.ebi.ac.uk/pdbsum/1i79 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1i79 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/i7/1i79_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=1i79 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
S-Adenosylmethionine decarboxylase belongs to a small class of amino acid decarboxylases that use a covalently bound pyruvate as a prosthetic group. It is an essential enzyme for polyamine biosynthesis and provides an important target for the design of anti-parasitic and cancer chemotherapeutic agents. We have determined the structures of S-adenosylmethionine decarboxylase complexed with the competitive inhibitors methylglyoxal bis(guanylhydrazone) and 4-amidinoindan-1-one-2'-amidinohydrazone as well as the irreversible inhibitors 5'-deoxy-5'-[N-methyl-N-[(2-aminooxy)ethyl]amino]adenosine, 5'-deoxy-5'-[N-methyl-N-(3-hydrazinopropyl)amino]adenosine, and the methyl ester analogue of S-adenosylmethionine. These structures elucidate residues important for substrate binding and show how those residues interact with both covalently and noncovalently bound inhibitors. S-Adenosylmethionine decarboxylase has a four-layer alphabeta betaalpha sandwich fold with residues from both beta-sheets contributing to substrate and inhibitor binding. The side chains of conserved residues Phe7, Phe223, and Glu247 and the backbone carbonyl of Leu65 play important roles in binding and positioning the ligands. The catalytically important residues Cys82, Ser229, and His243 are positioned near the methionyl group of the substrate. One molecule of putrescine per monomer is observed between the two beta-sheets but far away from the active site. The activating effects of putrescine may be due to conformational changes in the enzyme, to electrostatic effects, or both. The adenosyl moiety of the bound ligand is observed in the unusual syn conformation. The five structures reported here provide a framework for interpretation of S-adenosylmethionine decarboxylase inhibition data and suggest strategies for the development of more potent and more specific inhibitors of S-adenosylmethionine decarboxylase. | |||
The structural basis for substrate specificity and inhibition of human S-adenosylmethionine decarboxylase.,Tolbert WD, Ekstrom JL, Mathews II, Secrist JA 3rd, Kapoor P, Pegg AE, Ealick SE Biochemistry. 2001 Aug 14;40(32):9484-94. PMID:11583147<ref>PMID:11583147</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1i79" 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: Ealick | [[Category: Ealick SE]] | ||
[[Category: Ekstrom | [[Category: Ekstrom JL]] | ||
[[Category: Mathews II]] | |||
[[Category: Mathews | [[Category: Pegg AE]] | ||
[[Category: Pegg | [[Category: Secrist III JA]] | ||
[[Category: | [[Category: Tolbert WD]] | ||
[[Category: | |||
Latest revision as of 09:44, 30 October 2024
HUMAN S-ADENOSYLMETHIONINE DECARBOXYLASE WITH COVALENTLY BOUND PYRUVOYL GROUP AND COVALENTLY BOUND 5'-DEOXY-5'-[(3-HYDRAZINOPROPYL)METHYLAMINO]ADENOSINEHUMAN S-ADENOSYLMETHIONINE DECARBOXYLASE WITH COVALENTLY BOUND PYRUVOYL GROUP AND COVALENTLY BOUND 5'-DEOXY-5'-[(3-HYDRAZINOPROPYL)METHYLAMINO]ADENOSINE
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 belongs to a small class of amino acid decarboxylases that use a covalently bound pyruvate as a prosthetic group. It is an essential enzyme for polyamine biosynthesis and provides an important target for the design of anti-parasitic and cancer chemotherapeutic agents. We have determined the structures of S-adenosylmethionine decarboxylase complexed with the competitive inhibitors methylglyoxal bis(guanylhydrazone) and 4-amidinoindan-1-one-2'-amidinohydrazone as well as the irreversible inhibitors 5'-deoxy-5'-[N-methyl-N-[(2-aminooxy)ethyl]amino]adenosine, 5'-deoxy-5'-[N-methyl-N-(3-hydrazinopropyl)amino]adenosine, and the methyl ester analogue of S-adenosylmethionine. These structures elucidate residues important for substrate binding and show how those residues interact with both covalently and noncovalently bound inhibitors. S-Adenosylmethionine decarboxylase has a four-layer alphabeta betaalpha sandwich fold with residues from both beta-sheets contributing to substrate and inhibitor binding. The side chains of conserved residues Phe7, Phe223, and Glu247 and the backbone carbonyl of Leu65 play important roles in binding and positioning the ligands. The catalytically important residues Cys82, Ser229, and His243 are positioned near the methionyl group of the substrate. One molecule of putrescine per monomer is observed between the two beta-sheets but far away from the active site. The activating effects of putrescine may be due to conformational changes in the enzyme, to electrostatic effects, or both. The adenosyl moiety of the bound ligand is observed in the unusual syn conformation. The five structures reported here provide a framework for interpretation of S-adenosylmethionine decarboxylase inhibition data and suggest strategies for the development of more potent and more specific inhibitors of S-adenosylmethionine decarboxylase. The structural basis for substrate specificity and inhibition of human S-adenosylmethionine decarboxylase.,Tolbert WD, Ekstrom JL, Mathews II, Secrist JA 3rd, Kapoor P, Pegg AE, Ealick SE Biochemistry. 2001 Aug 14;40(32):9484-94. PMID:11583147[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
| ||||||||||||||||||