This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


2gd0

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: 200px<br /><applet load="2gd0" size="350" color="white" frame="true" align="right" spinBox="true" caption="2gd0, resolution 1.70&Aring;" /> '''The 1,1-proton trans...)
Current revision (08:48, 25 October 2023) (edit) (undo)
 
(14 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:2gd0.gif|left|200px]]<br /><applet load="2gd0" size="350" color="white" frame="true" align="right" spinBox="true"
 
-
caption="2gd0, resolution 1.70&Aring;" />
 
-
'''The 1,1-proton transfer reaction mechanism by alpha-methylacyl-CoA racemase is catalyzed by an aspartate/histidine pair and involves a smooth, methionine-rich surface for binding the fatty acyl moiety'''<br />
 
-
==Overview==
+
==The 1,1-proton transfer reaction mechanism by alpha-methylacyl-CoA racemase is catalyzed by an aspartate/histidine pair and involves a smooth, methionine-rich surface for binding the fatty acyl moiety==
-
alpha-Methylacyl-CoA racemases are essential enzymes for branched-chain, fatty acid metabolism. Their reaction mechanism and the structural basis, of their wide substrate specificity are poorly understood. High-resolution, crystal structures of Mycobacterium tuberculosis alpha-methylacyl-CoA, racemase (MCR) complexed with substrate molecules show the active site, geometry required for catalysis of the interconversion of (2S) and, (2R)-methylacyl-CoA. The thioester oxygen atom and the 2-methyl group are, in a cis-conformation with respect to each other. The thioester oxygen, atom fits into an oxyanion hole and the 2-methyl group points into a, hydrophobic pocket. The active site geometry agrees with a 1,1-proton, transfer mechanism in which the acid/base-pair residues are His126 and, Asp156. The structures of the complexes indicate that the acyl chains of, the S-substrate and the R-substrate bind in an S-pocket and an R-pocket, respectively. A unique feature of MCR is a large number of methionine, residues in the acyl binding region, located between the S-pocket and the, R-pocket. It appears that the (S) to (R) interconversion of the, 2-methylacyl chiral center is coupled to a movement of the acyl group over, this hydrophobic, methionine-rich surface, when moving from its S-pocket, to its R-pocket, whereas the 2-methyl moiety and the CoA group remain, fixed in their respective pockets.
+
<StructureSection load='2gd0' size='340' side='right'caption='[[2gd0]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[2gd0]] is a 4 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=2GD0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GD0 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]] 1.7&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MRS:(S)-2-METHYLMYRISTOYL-COENZYME+A'>MRS</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=2gd0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gd0 OCA], [https://pdbe.org/2gd0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gd0 RCSB], [https://www.ebi.ac.uk/pdbsum/2gd0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gd0 ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/AMACR_MYCTU AMACR_MYCTU] Catalyzes the epimerization of (2R)- and (2S)-methylacyl-coenzyme A (CoA) thioesters (PubMed:15632186, PubMed:19854148, PubMed:26348625). Accepts as substrates a wide range of alpha-methylacyl-CoAs, including (2R)-2-methylmyristoyl-CoA and (2S)-2-methylmyristoyl-CoA, (2R)-pristanoyl-CoA and (2S)-pristanoyl-CoA, and the cholesterol esters (25R)-3-oxo-cholest-4-en-26-oyl-CoA and (25S)-3-oxo-cholest-4-en-26-oyl-CoA (PubMed:15632186, PubMed:26348625). Can also catalyze the interconversion of the non-physiologic substrates (2R)-ibuprofenoyl-CoA and (2S)-ibuprofenoyl-CoA, which are potential competitive inhibitors of the enzyme (PubMed:19854148).<ref>PMID:15632186</ref> <ref>PMID:19854148</ref> <ref>PMID:26348625</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/gd/2gd0_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=2gd0 ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Alpha-methylacyl-CoA racemases are essential enzymes for branched-chain fatty acid metabolism. Their reaction mechanism and the structural basis of their wide substrate specificity are poorly understood. High-resolution crystal structures of Mycobacterium tuberculosis alpha-methylacyl-CoA racemase (MCR) complexed with substrate molecules show the active site geometry required for catalysis of the interconversion of (2S) and (2R)-methylacyl-CoA. The thioester oxygen atom and the 2-methyl group are in a cis-conformation with respect to each other. The thioester oxygen atom fits into an oxyanion hole and the 2-methyl group points into a hydrophobic pocket. The active site geometry agrees with a 1,1-proton transfer mechanism in which the acid/base-pair residues are His126 and Asp156. The structures of the complexes indicate that the acyl chains of the S-substrate and the R-substrate bind in an S-pocket and an R-pocket, respectively. A unique feature of MCR is a large number of methionine residues in the acyl binding region, located between the S-pocket and the R-pocket. It appears that the (S) to (R) interconversion of the 2-methylacyl chiral center is coupled to a movement of the acyl group over this hydrophobic, methionine-rich surface, when moving from its S-pocket to its R-pocket, whereas the 2-methyl moiety and the CoA group remain fixed in their respective pockets.
-
==About this Structure==
+
The catalysis of the 1,1-proton transfer by alpha-methyl-acyl-CoA racemase is coupled to a movement of the fatty acyl moiety over a hydrophobic, methionine-rich surface.,Bhaumik P, Schmitz W, Hassinen A, Hiltunen JK, Conzelmann E, Wierenga RK J Mol Biol. 2007 Apr 6;367(4):1145-61. Epub 2007 Jan 27. PMID:17320106<ref>PMID:17320106</ref>
-
2GD0 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 <scene name='pdbligand=MRS:'>MRS</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Alpha-methylacyl-CoA_racemase Alpha-methylacyl-CoA racemase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.1.99.4 5.1.99.4] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GD0 OCA].
+
-
==Reference==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
The Catalysis of the 1,1-Proton Transfer by alpha-Methyl-acyl-CoA Racemase Is Coupled to a Movement of the Fatty Acyl Moiety Over a Hydrophobic, Methionine-rich Surface., Bhaumik P, Schmitz W, Hassinen A, Hiltunen JK, Conzelmann E, Wierenga RK, J Mol Biol. 2007 Apr 6;367(4):1145-61. Epub 2007 Jan 27. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17320106 17320106]
+
</div>
-
[[Category: Alpha-methylacyl-CoA racemase]]
+
<div class="pdbe-citations 2gd0" style="background-color:#fffaf0;"></div>
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Mycobacterium tuberculosis]]
-
[[Category: Single protein]]
+
[[Category: Bhaumik P]]
-
[[Category: Bhaumik, P.]]
+
[[Category: Wierenga RK]]
-
[[Category: Wierenga, R.K.]]
+
-
[[Category: GOL]]
+
-
[[Category: MRS]]
+
-
[[Category: alpha-methylacyl-coa racemase]]
+
-
[[Category: coa transferase]]
+
-
[[Category: coenzyme a]]
+
-
[[Category: proton transfer]]
+
-
[[Category: racemase]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jan 29 19:56:50 2008''
+

Current revision

The 1,1-proton transfer reaction mechanism by alpha-methylacyl-CoA racemase is catalyzed by an aspartate/histidine pair and involves a smooth, methionine-rich surface for binding the fatty acyl moiety

PDB ID 2gd0

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2gd0"
Personal tools