View source for 2p2m


==Acetyl-CoA Synthetase, R194A mutation==
<StructureSection load='2p2m' size='340' side='right'caption='[[2p2m]], [[Resolution|resolution]] 2.11&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2p2m]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P2M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2P2M FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PRX:ADENOSINE-5-MONOPHOSPHATE-PROPYL+ESTER'>PRX</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1pg4|1pg4]], [[1ry2|1ry2]], [[1t5d|1t5d]], [[2p20|2p20]], [[2p2b|2p2b]], [[2p2f|2p2f]], [[2p2j|2p2j]], [[2p2q|2p2q]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Acetate--CoA_ligase Acetate--CoA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.2.1.1 6.2.1.1] </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=2p2m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p2m OCA], [http://pdbe.org/2p2m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2p2m RCSB], [http://www.ebi.ac.uk/pdbsum/2p2m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2p2m ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/ACSA_SALTY ACSA_SALTY]] Catalyzes the conversion of acetate into acetyl-CoA (AcCoA), an essential intermediate at the junction of anabolic and catabolic pathways. Acs undergoes a two-step reaction. In the first half reaction, Acs combines acetate with ATP to form acetyl-adenylate (AcAMP) intermediate. In the second half reaction, it can then transfer the acetyl group from AcAMP to the sulfhydryl group of CoA, forming the product AcCoA.<ref>PMID:17497934</ref>   Enables the cell to use acetate during aerobic growth to generate energy via the TCA cycle, and biosynthetic compounds via the glyoxylate shunt. Acetylates CheY, the response regulator involved in flagellar movement and chemotaxis (By similarity).<ref>PMID:17497934</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/p2/2p2m_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=2p2m ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The adenylate-forming enzymes, including acyl-CoA synthetases, the adenylation domains of non-ribosomal peptide synthetases (NRPS), and firefly luciferase, perform two half-reactions in a ping-pong mechanism. We have proposed a domain alternation mechanism for these enzymes whereby, upon completion of the initial adenylation reaction, the C-terminal domain of these enzymes undergoes a 140 degrees rotation to perform the second thioester-forming half-reaction. Structural and kinetic data of mutant enzymes support this hypothesis. We present here mutations to Salmonella enterica acetyl-CoA synthetase (Acs) and test the ability of the enzymes to catalyze the complete reaction and the adenylation half-reaction. Substitution of Lys609 with alanine results in an enzyme that is unable to catalyze the adenylate reaction, while the Gly524 to leucine substitution is unable to catalyze the complete reaction yet catalyzes the adenylation half-reaction with activity comparable to the wild-type enzyme. The positions of these two residues, which are located on the mobile C-terminal domain, strongly support the domain alternation hypothesis. We also present steady-state kinetic data of putative substrate-binding residues and demonstrate that no single residue plays a dominant role in dictating CoA binding. We have also created two mutations in the active site to alter the acyl substrate specificity. Finally, the crystallographic structures of wild-type Acs and mutants R194A, R584A, R584E, K609A, and V386A are presented to support the biochemical analysis.

Biochemical and crystallographic analysis of substrate binding and conformational changes in acetyl-CoA synthetase.,Reger AS, Carney JM, Gulick AM Biochemistry. 2007 Jun 5;46(22):6536-46. Epub 2007 May 12. PMID:17497934<ref>PMID:17497934</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2p2m" style="background-color:#fffaf0;"></div>

==See Also==
*[[Acetyl-CoA synthetase 3D structures|Acetyl-CoA synthetase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Acetate--CoA ligase]]
[[Category: Large Structures]]
[[Category: Gulick, A M]]
[[Category: Reger, A S]]
[[Category: Acyl-coa ligase]]
[[Category: Adenylate-forming enzyme]]
[[Category: Domain alternation]]
[[Category: Ligase]]