2xbn

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{{Seed}}
 
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[[Image:2xbn.png|left|200px]]
 
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==Inhibition of the PLP-dependent enzyme serine palmitoyltransferase by cycloserine: evidence for a novel decarboxylative mechanism of inactivation==
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The line below this paragraph, containing "STRUCTURE_2xbn", creates the "Structure Box" on the page.
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<StructureSection load='2xbn' size='340' side='right'caption='[[2xbn]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2xbn]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Sphingomonas_paucimobilis Sphingomonas paucimobilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XBN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XBN FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.4&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PMP:4-DEOXY-4-AMINOPYRIDOXAL-5-PHOSPHATE'>PMP</scene></td></tr>
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{{STRUCTURE_2xbn| PDB=2xbn | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2xbn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xbn OCA], [https://pdbe.org/2xbn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xbn RCSB], [https://www.ebi.ac.uk/pdbsum/2xbn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xbn ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/SPT_SPHPI SPT_SPHPI] Catalyzes the condensation of L-serine with palmitoyl-CoA (hexadecanoyl-CoA) to produce 3-oxosphinganine (PubMed:11279212, PubMed:17557831, PubMed:17559874, PubMed:19376777). Exhibits a broad substrate specificity concerning the chain length and the degree of unsaturation of acyl-CoA (PubMed:11279212, PubMed:19376777).<ref>PMID:11279212</ref> <ref>PMID:17557831</ref> <ref>PMID:17559874</ref> <ref>PMID:19376777</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xb/2xbn_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2xbn ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Cycloserine (CS, 4-amino-3-isoxazolidone) is a cyclic amino acid mimic that is known to inhibit many essential pyridoxal 5'-phosphate (PLP)-dependent enzymes. Two CS enantiomers are known; d-cycloserine (DCS, also known as Seromycin) is a natural product that is used to treat resistant Mycobacterium tuberculosis infections as well as neurological disorders since it is a potent NMDA receptor agonist, and l-cycloserine (LCS) is a synthetic enantiomer whose usefulness as a drug has been hampered by its inherent toxicity arising through inhibition of sphingolipid metabolism. Previous studies on various PLP-dependent enzymes revealed a common mechanism of inhibition by both enantiomers of CS; the PLP cofactor is disabled by forming a stable 3-hydroxyisoxazole/pyridoxamine 5'-phosphate (PMP) adduct at the active site where the cycloserine ring remains intact. Here we describe a novel mechanism of CS inactivation of the PLP-dependent enzyme serine palmitoyltransferase (SPT) from Sphingomonas paucimobilis. SPT catalyses the condensation of l-serine and palmitoyl-CoA, the first step in the de novo sphingolipid biosynthetic pathway. We have used a range of kinetic, spectroscopic and structural techniques to postulate that both LCS and DCS inactivate SPT by transamination to form a free pyridoxamine 5'-phosphate (PMP) and beta-aminooxyacetaldehyde that remain bound at the active site. We suggest this occurs by ring opening of the cycloserine ring followed by decarboxylation. Enzyme kinetics show that inhibition is reversed by incubation with excess PLP and that LCS is a more effective SPT inhibitor than DCS. UV-visible spectroscopic data, combined with site-directed mutagenesis, suggest that a mobile Arg(378) residue is involved in cycloserine inactivation of SPT.
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===INHIBITION OF THE PLP-DEPENDENT ENZYME SERINE PALMITOYLTRANSFERASE BY CYCLOSERINE: EVIDENCE FOR A NOVEL DECARBOXYLATIVE MECHANISM OF INACTIVATION===
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Inhibition of the PLP-dependent enzyme serine palmitoyltransferase by cycloserine: evidence for a novel decarboxylative mechanism of inactivation.,Lowther J, Yard BA, Johnson KA, Carter LG, Bhat VT, Raman MC, Clarke DJ, Ramakers B, McMahon SA, Naismith JH, Campopiano DJ Mol Biosyst. 2010 May 5. PMID:20445930<ref>PMID:20445930</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2xbn" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_20445930}}, adds the Publication Abstract to the page
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*[[Serine palmitoyltransferase 3D structures|Serine palmitoyltransferase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 20445930 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_20445930}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[Category: Large Structures]]
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2XBN is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Sphingomonas_paucimobilis Sphingomonas paucimobilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XBN OCA].
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==Reference==
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<ref group="xtra">PMID:20445930</ref><references group="xtra"/>
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[[Category: Sphingomonas paucimobilis]]
[[Category: Sphingomonas paucimobilis]]
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[[Category: Bhat, V T.]]
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[[Category: Bhat VT]]
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[[Category: Campopiano, D J.]]
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[[Category: Campopiano DJ]]
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[[Category: Carter, L G.]]
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[[Category: Carter LG]]
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[[Category: Clarke, D J.]]
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[[Category: Clarke DJ]]
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[[Category: Johnson, K A.]]
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[[Category: Johnson KA]]
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[[Category: Lowther, J.]]
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[[Category: Lowther J]]
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[[Category: Mcmahon, S A.]]
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[[Category: McMahon SA]]
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[[Category: Naismith, J H.]]
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[[Category: Naismith JH]]
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[[Category: Ramakers, B.]]
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[[Category: Ramakers B]]
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[[Category: Raman, M C.C.]]
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[[Category: Raman MCC]]
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[[Category: Yard, B A.]]
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[[Category: Yard BA]]
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[[Category: Pyridoxal phosphate]]
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[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 7 07:49:31 2010''
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Current revision

Inhibition of the PLP-dependent enzyme serine palmitoyltransferase by cycloserine: evidence for a novel decarboxylative mechanism of inactivation

PDB ID 2xbn

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