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4rcg

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Revision as of 06:49, 2 March 2023

Crystal Structure Analysis of MTB PEPCK without Mn+2

Structural highlights

4rcg is a 1 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PCKG_MYCTU Involved in the gluconeogenesis, in growth on fatty acids and is important for initiation of infection in the macrophages. Catalyzes the GTP-dependent conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle.^[1] ^[2]

Publication Abstract from PubMed

Tuberculosis, the second leading infectious disease killer after HIV, remains a top public health priority. The causative agent of tuberculosis, Mycobacterium tuberculosis (Mtb), which can cause both acute and clinically latent infections, reprograms metabolism in response to the host niche. Phosphoenolpyruvate carboxykinase (Pck) is the enzyme at the center of the phosphoenolpyruvate-pyruvate-oxaloacetate node, which is involved in regulating the carbon flow distribution to catabolism, anabolism, or respiration in different states of Mtb infection. Under standard growth conditions, Mtb Pck is associated with gluconeogenesis and catalyzes the metal-dependent formation of phosphoenolpyruvate. In non-replicating Mtb, Pck can catalyze anaplerotic biosynthesis of oxaloacetate. Here, we present insights into the regulation of Mtb Pck activity by divalent cations. Through analysis of the X-ray structure of Pck-GDP and Pck-GDP-Mn2+ complexes, mutational analysis of the GDP binding site, and quantum mechanical (QM)-based analysis, we explored the structural determinants of efficient Mtb Pck catalysis. We demonstrate that Mtb Pck requires presence of Mn2+ and Mg2+ cations for efficient catalysis of gluconeogenic and anaplerotic reactions. The anaplerotic reaction, which preferably functions in reducing conditions that are characteristic for slowed or stopped Mtb replication, is also effectively activated by Fe2+ in the presence of Mn2+ or Mg2+ cations. In contrast, simultaneous presence of Fe2+ and Mn2+ or Mg2+ inhibits the gluconeogenic reaction. These results suggest that inorganic ions can contribute to regulation of central carbon metabolism by influencing the activity of Pck. Furthermore, the X-ray structure determination, biochemical characterization, and QM analysis of Pck mutants confirmed the important role of the Phe triad for proper binding of the GDP-Mn2+ complex in the nucleotide binding site and efficient catalysis of the anaplerotic reaction.

Structural and Functional Studies of Phosphoenolpyruvate Carboxykinase from Mycobacterium tuberculosis.,Machova I, Snasel J, Dostal J, Brynda J, Fanfrlik J, Singh M, Tarabek J, Vanek O, Bednarova L, Pichova I PLoS One. 2015 Mar 23;10(3):e0120682. doi: 10.1371/journal.pone.0120682., eCollection 2015. PMID:25798914^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Liu K, Ba X, Yu J, Li J, Wei Q, Han G, Li G, Cui Y. The phosphoenolpyruvate carboxykinase of Mycobacterium tuberculosis induces strong cell-mediated immune responses in mice. Mol Cell Biochem. 2006 Aug;288(1-2):65-71. PMID:16691317 doi:10.1007/s11010-006-9119-5
↑ Marrero J, Rhee KY, Schnappinger D, Pethe K, Ehrt S. Gluconeogenic carbon flow of tricarboxylic acid cycle intermediates is critical for Mycobacterium tuberculosis to establish and maintain infection. Proc Natl Acad Sci U S A. 2010 May 25;107(21):9819-24. PMID:20439709 doi:10.1073/pnas.1000715107
↑ Machova I, Snasel J, Dostal J, Brynda J, Fanfrlik J, Singh M, Tarabek J, Vanek O, Bednarova L, Pichova I. Structural and Functional Studies of Phosphoenolpyruvate Carboxykinase from Mycobacterium tuberculosis. PLoS One. 2015 Mar 23;10(3):e0120682. doi: 10.1371/journal.pone.0120682., eCollection 2015. PMID:25798914 doi:http://dx.doi.org/10.1371/journal.pone.0120682

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4rcg"

@@ Line 3: / Line 3: @@
 <StructureSection load='4rcg' size='340' side='right'caption='[[4rcg]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4rcg]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RCG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RCG FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4rcg]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RCG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RCG FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4r43|4r43]]</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=4rcg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rcg OCA], [https://pdbe.org/4rcg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rcg RCSB], [https://www.ebi.ac.uk/pdbsum/4rcg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rcg ProSAT]</span></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pckG, P425_00220, RVBD_0211 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphoenolpyruvate_carboxykinase_(GTP) Phosphoenolpyruvate carboxykinase (GTP)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.32 4.1.1.32] </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=4rcg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rcg OCA], [http://pdbe.org/4rcg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rcg RCSB], [http://www.ebi.ac.uk/pdbsum/4rcg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rcg ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/I6Y334_MYCTU I6Y334_MYCTU]] Catalyzes the conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle.[HAMAP-Rule:MF_00452]
+[https://www.uniprot.org/uniprot/PCKG_MYCTU PCKG_MYCTU] Involved in the gluconeogenesis, in growth on fatty acids and is important for initiation of infection in the macrophages. Catalyzes the GTP-dependent conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle.<ref>PMID:16691317</ref> <ref>PMID:20439709</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 20: @@
 ==See Also==
-*[[Phosphoenolpyruvate carboxykinase|Phosphoenolpyruvate carboxykinase]]
+*[[Phosphoenolpyruvate carboxykinase 3D structures|Phosphoenolpyruvate carboxykinase 3D structures]]
 == References ==
 <references/>
@@ Line 29: / Line 26: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Myctu]]
+[[Category: Mycobacterium tuberculosis H37Rv]]
-[[Category: Brynda, J]]
+[[Category: Brynda J]]
-[[Category: Dostal, J]]
+[[Category: Dostal J]]
-[[Category: Fanfrlik, J]]
+[[Category: Fanfrlik J]]
-[[Category: Machova, I]]
+[[Category: Machova I]]
-[[Category: Pichova, I]]
+[[Category: Pichova I]]
-[[Category: Snasel, J]]
+[[Category: Snasel J]]
-[[Category: Lyase]]
-[[Category: Phosphoenolpyruvate carboxykinase]]

4rcg

From Proteopedia

Revision as of 06:49, 2 March 2023

Crystal Structure Analysis of MTB PEPCK without Mn+2

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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