1l1e: Difference between revisions

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New page: left|200px<br /><applet load="1l1e" size="450" color="white" frame="true" align="right" spinBox="true" caption="1l1e, resolution 2.0Å" /> '''Crystal Structure of ...
 
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[[Image:1l1e.gif|left|200px]]<br /><applet load="1l1e" size="450" color="white" frame="true" align="right" spinBox="true"
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'''Crystal Structure of Mycolic Acid Cyclopropane Synthase PcaA Complexed with S-adenosyl-L-homocysteine'''<br />


==Overview==
==Crystal Structure of Mycolic Acid Cyclopropane Synthase PcaA Complexed with S-adenosyl-L-homocysteine==
Mycolic acids are major components of the cell wall of Mycobacterium, tuberculosis. Several studies indicate that functional groups in the acyl, chain of mycolic acids are important for pathogenesis and persistence., There are at least three mycolic acid cyclopropane synthases (PcaA, CmaA1, and CmaA2) that are responsible for these site-specific modifications of, mycolic acids. To derive information on the specificity and enzyme, mechanism of the family of proteins, the crystal structures of CmaA1, CmaA2, and PcaA were solved to 2-, 2-, and 2.65-A resolution, respectively. All three enzymes have a seven-stranded alpha/beta fold, similar to other methyltransferases with the location and interactions, with the cofactor S-adenosyl-l-methionine conserved. The structures of the, ternary complexes demonstrate the position of the mycolic acid substrate, binding site. Close examination of the active site reveals electron, density that we believe represents a bicarbonate ion. The structures, support the hypothesis that these enzymes catalyze methyl transfer via a, carbocation mechanism in which the bicarbonate ion acts as a general base., In addition, comparison of the enzyme structures reveals a possible, mechanism for substrate specificity. These structures provide a foundation, for rational-drug design, which may lead to the development of new, inhibitors effective against persistent bacteria.
<StructureSection load='1l1e' size='340' side='right'caption='[[1l1e]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 
== Structural highlights ==
==About this Structure==
<table><tr><td colspan='2'>[[1l1e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L1E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1L1E FirstGlance]. <br>
1L1E is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with CO3 and SAH as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Cyclopropane-fatty-acyl-phospholipid_synthase Cyclopropane-fatty-acyl-phospholipid synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.79 2.1.1.79] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1L1E OCA].  
</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&#8491;</td></tr>
 
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></td></tr>
==Reference==
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1l1e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l1e OCA], [https://pdbe.org/1l1e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1l1e RCSB], [https://www.ebi.ac.uk/pdbsum/1l1e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1l1e ProSAT], [https://www.topsan.org/Proteins/TBSGC/1l1e TOPSAN]</span></td></tr>
Crystal structures of mycolic acid cyclopropane synthases from Mycobacterium tuberculosis., Huang CC, Smith CV, Glickman MS, Jacobs WR Jr, Sacchettini JC, J Biol Chem. 2002 Mar 29;277(13):11559-69. Epub 2001 Dec 26. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11756461 11756461]
</table>
[[Category: Cyclopropane-fatty-acyl-phospholipid synthase]]
== Function ==
[https://www.uniprot.org/uniprot/CMAS3_MYCTU CMAS3_MYCTU] Involved in the phagosome maturation block (PMB). Catalyzes the conversion of a double bond to a cyclopropane ring at the proximal position of an alpha mycolic acid via the transfer of a methylene group from S-adenosyl-L-methionine. It can use cis, cis 11,14-eicosadienoic acid and linoelaidic acid as substrate. Cyclopropanated mycolic acids are key factors participating in cell envelope permeability, host immunomodulation and persistence.<ref>PMID:10882107</ref> <ref>PMID:22621931</ref>
== 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/l1/1l1e_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/main_output.php?pdb_ID=1l1e ConSurf].
<div style="clear:both"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Single protein]]
[[Category: Glickman MS]]
[[Category: Glickman, M.S.]]
[[Category: Huang C-C]]
[[Category: Huang, C.C.]]
[[Category: Jacobs Jr WR]]
[[Category: Jr., W.R.Jacobs.]]
[[Category: Sacchettini JC]]
[[Category: Sacchettini, J.C.]]
[[Category: Smith CV]]
[[Category: Smith, C.V.]]
[[Category: TBSGC, TB.Structural.Genomics.Consortium.]]
[[Category: CO3]]
[[Category: SAH]]
[[Category: alpha/beta]]
[[Category: methyltransferase]]
[[Category: protein structure initiative]]
[[Category: psi]]
[[Category: s-adenosyl-l-homocysteine cofactor]]
[[Category: structural genomics]]
[[Category: tb structural genomics consortium]]
[[Category: tbsgc]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 25 02:18:03 2007''

Latest revision as of 10:29, 14 February 2024

Crystal Structure of Mycolic Acid Cyclopropane Synthase PcaA Complexed with S-adenosyl-L-homocysteineCrystal Structure of Mycolic Acid Cyclopropane Synthase PcaA Complexed with S-adenosyl-L-homocysteine

Structural highlights

1l1e is a 2 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT, TOPSAN

Function

CMAS3_MYCTU Involved in the phagosome maturation block (PMB). Catalyzes the conversion of a double bond to a cyclopropane ring at the proximal position of an alpha mycolic acid via the transfer of a methylene group from S-adenosyl-L-methionine. It can use cis, cis 11,14-eicosadienoic acid and linoelaidic acid as substrate. Cyclopropanated mycolic acids are key factors participating in cell envelope permeability, host immunomodulation and persistence.[1] [2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

  1. ↑ Glickman MS, Cox JS, Jacobs WR Jr. A novel mycolic acid cyclopropane synthetase is required for cording, persistence, and virulence of Mycobacterium tuberculosis. Mol Cell. 2000 Apr;5(4):717-27. PMID:10882107 doi:10.1016/s1097-2765(00)80250-6
  2. ↑ Corrales RM, Molle V, Leiba J, Mourey L, de Chastellier C, Kremer L. Phosphorylation of mycobacterial PcaA inhibits mycolic acid cyclopropanation: consequences for intracellular survival and for phagosome maturation block. J Biol Chem. 2012 Jul 27;287(31):26187-99. PMID:22621931 doi:10.1074/jbc.M112.373209

1l1e, resolution 2.00Å

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