7odc: Difference between revisions
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==CRYSTAL STRUCTURE ORNITHINE DECARBOXYLASE FROM MOUSE, TRUNCATED 37 RESIDUES FROM THE C-TERMINUS, TO 1.6 ANGSTROM RESOLUTION== | |||
<StructureSection load='7odc' size='340' side='right' caption='[[7odc]], [[Resolution|resolution]] 1.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7odc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ODC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=7ODC FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ornithine_decarboxylase Ornithine decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.17 4.1.1.17] </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=7odc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7odc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=7odc RCSB], [http://www.ebi.ac.uk/pdbsum/7odc PDBsum]</span></td></tr> | |||
</table> | |||
== 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/od/7odc_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
BACKGROUND: Pyridoxal-5'-phosphate (PLP) dependent enzymes catalyze a broad range of reactions, resulting in bond cleavage at C alpha, C beta, or C gamma carbons of D and L amino acid substrates. Ornithine decarboxylase (ODC) is a PLP-dependent enzyme that controls a critical step in the biosynthesis of polyamines, small organic polycations whose controlled levels are essential for proper growth. ODC inhibition has applications for the treatment of certain cancers and parasitic ailments such as African sleeping sickness. RESULTS: The structure of truncated mouse ODC (mODC') was determined by multiple isomorphous replacement methods and refined to 1.6 A resolution. This is the first structure of a Group IV decarboxylase. The monomer contains two domains: an alpha/beta barrel that binds the cofactor, and a second domain consisting mostly of beta structure. Only the dimer is catalytically active, as the active sites are constructed of residues from both monomers. The interactions stabilizing the dimer shed light on its regulation by antizyme. The overall structure and the environment of the cofactor are compared with those of alanine racemase. CONCLUSIONS: The analysis of the mODC' structure and its comparison with alanine racemase, together with modeling studies of the external aldimine intermediate, provide insight into the stereochemical characteristics of PLP-dependent decarboxylation. The structure comparison reveals stereochemical differences with other PLP-dependent enzymes and the bacterial ODC. These characteristics may be exploited in the design of new inhibitors specific for eukaryotic and bacterial ODCs, and provide the basis for a detailed understanding of the mechanism by which these enzymes regulate reaction specificity. | |||
Structure of mammalian ornithine decarboxylase at 1.6 A resolution: stereochemical implications of PLP-dependent amino acid decarboxylases.,Kern AD, Oliveira MA, Coffino P, Hackert ML Structure. 1999 May;7(5):567-81. PMID:10378276<ref>PMID:10378276</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
| Line 11: | Line 31: | ||
*[[Ornithine decarboxylase|Ornithine decarboxylase]] | *[[Ornithine decarboxylase|Ornithine decarboxylase]] | ||
*[[Quinone reductase|Quinone reductase]] | *[[Quinone reductase|Quinone reductase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Ornithine decarboxylase]] | [[Category: Ornithine decarboxylase]] | ||
[[Category: Coffino, P | [[Category: Coffino, P]] | ||
[[Category: Hackert, M L | [[Category: Hackert, M L]] | ||
[[Category: Kern, A D | [[Category: Kern, A D]] | ||
[[Category: Oliveira, M A | [[Category: Oliveira, M A]] | ||
[[Category: A/b-barrel]] | [[Category: A/b-barrel]] | ||
[[Category: Chemotherapy target]] | [[Category: Chemotherapy target]] | ||
Revision as of 11:37, 18 December 2014
CRYSTAL STRUCTURE ORNITHINE DECARBOXYLASE FROM MOUSE, TRUNCATED 37 RESIDUES FROM THE C-TERMINUS, TO 1.6 ANGSTROM RESOLUTIONCRYSTAL STRUCTURE ORNITHINE DECARBOXYLASE FROM MOUSE, TRUNCATED 37 RESIDUES FROM THE C-TERMINUS, TO 1.6 ANGSTROM RESOLUTION
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 PubMedBACKGROUND: Pyridoxal-5'-phosphate (PLP) dependent enzymes catalyze a broad range of reactions, resulting in bond cleavage at C alpha, C beta, or C gamma carbons of D and L amino acid substrates. Ornithine decarboxylase (ODC) is a PLP-dependent enzyme that controls a critical step in the biosynthesis of polyamines, small organic polycations whose controlled levels are essential for proper growth. ODC inhibition has applications for the treatment of certain cancers and parasitic ailments such as African sleeping sickness. RESULTS: The structure of truncated mouse ODC (mODC') was determined by multiple isomorphous replacement methods and refined to 1.6 A resolution. This is the first structure of a Group IV decarboxylase. The monomer contains two domains: an alpha/beta barrel that binds the cofactor, and a second domain consisting mostly of beta structure. Only the dimer is catalytically active, as the active sites are constructed of residues from both monomers. The interactions stabilizing the dimer shed light on its regulation by antizyme. The overall structure and the environment of the cofactor are compared with those of alanine racemase. CONCLUSIONS: The analysis of the mODC' structure and its comparison with alanine racemase, together with modeling studies of the external aldimine intermediate, provide insight into the stereochemical characteristics of PLP-dependent decarboxylation. The structure comparison reveals stereochemical differences with other PLP-dependent enzymes and the bacterial ODC. These characteristics may be exploited in the design of new inhibitors specific for eukaryotic and bacterial ODCs, and provide the basis for a detailed understanding of the mechanism by which these enzymes regulate reaction specificity. Structure of mammalian ornithine decarboxylase at 1.6 A resolution: stereochemical implications of PLP-dependent amino acid decarboxylases.,Kern AD, Oliveira MA, Coffino P, Hackert ML Structure. 1999 May;7(5):567-81. PMID:10378276[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also
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