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.


1x74

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (13:36, 13 March 2024) (edit) (undo)
 
(12 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1x74.gif|left|200px]]
 
-
{{Structure
+
==Alpha-methylacyl-CoA racemase from Mycobacterium tuberculosis- mutational and structural characterization of the fold and active site==
-
|PDB= 1x74 |SIZE=350|CAPTION= <scene name='initialview01'>1x74</scene>, resolution 1.79&Aring;
+
<StructureSection load='1x74' size='340' side='right'caption='[[1x74]], [[Resolution|resolution]] 1.79&Aring;' scene=''>
-
|SITE=
+
== Structural highlights ==
-
|LIGAND= <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>
+
<table><tr><td colspan='2'>[[1x74]] 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=1X74 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1X74 FirstGlance]. <br>
-
|ACTIVITY= [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]
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.79&#8491;</td></tr>
-
|GENE=
+
<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=PO4:PHOSPHATE+ION'>PO4</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=1x74 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1x74 OCA], [https://pdbe.org/1x74 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1x74 RCSB], [https://www.ebi.ac.uk/pdbsum/1x74 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1x74 ProSAT]</span></td></tr>
-
 
+
</table>
-
'''Alpha-methylacyl-CoA racemase from Mycobacterium tuberculosis- mutational and structural characterization of the fold and active site'''
+
== 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 ==
-
==Overview==
+
[[Image:Consurf_key_small.gif|200px|right]]
-
Alpha-methylacyl-CoA racemase (Amacr) catalyzes the racemization of alpha-methyl-branched CoA esters. Sequence comparisons have shown that this enzyme is a member of the family III CoA transferases. The mammalian Amacr is involved in bile acid synthesis and branched-chain fatty acid degradation. In human, mutated variants of Amacr have been shown to be associated with disease states. Amino acid sequence alignment of Amacrs and its homologues from various species revealed 26 conserved protic residues, assumed to be potential candidates as catalytic residues. Amacr from Mycobacterium tuberculosis (MCR) was taken as a representative of the racemases. To determine their importance for efficient catalysis, each of these 26 protic residues of MCR was mutated into an alanine, respectively, and the mutated variants were overexpressed in Escherichia coli. It was found that four variants (R91A, H126A, D156A, and E241A) were properly folded but had much decreased catalytic efficiency. Apparently, Arg91, His126, Asp156, and Glu241 are important catalytic residues of MCR. The importance of these residues for catalysis can be rationalized by the 1.8 A resolution crystal structure of MCR, which shows that the catalytic site is at the interface between the large and small domain of two different subunits of the dimeric enzyme. This crystal structure is the first structure of a complete enzyme of the bile acid synthesis pathway. It shows that MCR has unique structural features, not seen in the structures of the sequence related formyl-CoA transferases, suggesting that the family III CoA transferases can be subdivided in at least two classes, being racemases and CoA transferases.
+
Check<jmol>
-
 
+
<jmolCheckbox>
-
==About this Structure==
+
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/x7/1x74_consurf.spt"</scriptWhenChecked>
-
1X74 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1X74 OCA].
+
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
-
 
+
<text>to colour the structure by Evolutionary Conservation</text>
-
==Reference==
+
</jmolCheckbox>
-
Alpha-methylacyl-CoA racemase from Mycobacterium tuberculosis. Mutational and structural characterization of the active site and the fold., Savolainen K, Bhaumik P, Schmitz W, Kotti TJ, Conzelmann E, Wierenga RK, Hiltunen JK, J Biol Chem. 2005 Apr 1;280(13):12611-20. Epub 2005 Jan 4. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15632186 15632186]
+
</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=1x74 ConSurf].
-
[[Category: Alpha-methylacyl-CoA racemase]]
+
<div style="clear:both"></div>
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Mycobacterium tuberculosis]]
-
[[Category: Single protein]]
+
[[Category: Bhaumik P]]
-
[[Category: Bhaumik, P.]]
+
[[Category: Conzelmann E]]
-
[[Category: Conzelmann, E.]]
+
[[Category: Hiltunen JK]]
-
[[Category: Hiltunen, J K.]]
+
[[Category: Kalle S]]
-
[[Category: Kalle, S.]]
+
[[Category: Kotti TJ]]
-
[[Category: Kotti, T J.]]
+
[[Category: Schmitz W]]
-
[[Category: Schmitz, W.]]
+
[[Category: Wierenga RK]]
-
[[Category: Wierenga, R K.]]
+
-
[[Category: GOL]]
+
-
[[Category: PO4]]
+
-
[[Category: alpha-methylacyl-coa racemase]]
+
-
[[Category: coa transferase]]
+
-
[[Category: coenzyme some]]
+
-
[[Category: racemase]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:05:53 2008''
+

Current revision

Alpha-methylacyl-CoA racemase from Mycobacterium tuberculosis- mutational and structural characterization of the fold and active site

PDB ID 1x74

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/1x74"
Personal tools