2p20: Difference between revisions

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New page: left|200px<br /><applet load="2p20" size="450" color="white" frame="true" align="right" spinBox="true" caption="2p20, resolution 2.220Å" /> '''Acetyl-CoA Syntheta...
 
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caption="2p20, resolution 2.220&Aring;" />
'''Acetyl-CoA Synthetase, R584A mutation'''<br />


==Overview==
==Acetyl-CoA Synthetase, R584A mutation==
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.
<StructureSection load='2p20' size='340' side='right'caption='[[2p20]], [[Resolution|resolution]] 2.22&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2p20]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Salmonella_enterica_subsp._enterica_serovar_Typhimurium Salmonella enterica subsp. enterica serovar Typhimurium]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P20 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2P20 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.22&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PRX:ADENOSINE-5-MONOPHOSPHATE-PROPYL+ESTER'>PRX</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=2p20 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p20 OCA], [https://pdbe.org/2p20 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2p20 RCSB], [https://www.ebi.ac.uk/pdbsum/2p20 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2p20 ProSAT]</span></td></tr>
</table>
== Function ==
[https://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/p2/2p20_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=2p20 ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
2P20 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Salmonella_typhimurium Salmonella typhimurium] with PRX as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2P20 OCA].
*[[Acetyl-CoA synthetase 3D structures|Acetyl-CoA synthetase 3D structures]]
 
== References ==
==Reference==
<references/>
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17497934 17497934]
__TOC__
[[Category: Acetate--CoA ligase]]
</StructureSection>
[[Category: Salmonella typhimurium]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Salmonella enterica subsp. enterica serovar Typhimurium]]
[[Category: Gulick, A.M.]]
[[Category: Gulick AM]]
[[Category: Reger, A.S.]]
[[Category: Reger AS]]
[[Category: PRX]]
[[Category: acyl-coa ligase]]
[[Category: adenylate-forming enzymes]]
[[Category: domain alternation]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 13:23:19 2007''

Latest revision as of 16:53, 13 March 2024

Acetyl-CoA Synthetase, R584A mutationAcetyl-CoA Synthetase, R584A mutation

Structural highlights

2p20 is a 2 chain structure with sequence from Salmonella enterica subsp. enterica serovar Typhimurium. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.22Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.[1] 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).[2]

Evolutionary Conservation

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

See Also

References

  1. ↑ Reger AS, Carney JM, Gulick AM. Biochemical and crystallographic analysis of substrate binding and conformational changes in acetyl-CoA synthetase. Biochemistry. 2007 Jun 5;46(22):6536-46. Epub 2007 May 12. PMID:17497934 doi:http://dx.doi.org/10.1021/bi6026506
  2. ↑ Reger AS, Carney JM, Gulick AM. Biochemical and crystallographic analysis of substrate binding and conformational changes in acetyl-CoA synthetase. Biochemistry. 2007 Jun 5;46(22):6536-46. Epub 2007 May 12. PMID:17497934 doi:http://dx.doi.org/10.1021/bi6026506

2p20, resolution 2.22Å

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