5djh: Difference between revisions
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The | ==Structure of M. tuberculosis CysQ, a PAP phosphatase with AMP, PO4, and 3Mg bound== | ||
<StructureSection load='5djh' size='340' side='right'caption='[[5djh]], [[Resolution|resolution]] 1.45Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5djh]] is a 1 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=5DJH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DJH 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]] 1.451Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=5djh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5djh OCA], [https://pdbe.org/5djh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5djh RCSB], [https://www.ebi.ac.uk/pdbsum/5djh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5djh ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CYSQ_MYCTU CYSQ_MYCTU] Phosphatase with a broad specificity. Its primary physiological function is to dephosphorylate 3'-phosphoadenosine 5'-phosphate (PAP) and 3'-phosphoadenosine 5'-phosphosulfate (PAPS). Thus, plays a role in mycobacterial sulfur metabolism, since it can serve as a key regulator of the sulfate assimilation pathway by controlling the pools of PAP and PAPS in the cell. To a lesser extent, is also able to hydrolyze inositol 1-phosphate (I-1-P), fructose 1,6-bisphosphate (FBP) (to fructose 6-phosphate (F-6-P)) and AMP in vitro, but this might not be significant in vivo. Glucose-1-phosphate (G-1-P), p-nitrophenyl phosphate (pNPP), and beta-glycerol phosphate (beta-GP) are also good substrates, compared to I-1-P. With much lower efficiency, can also hydrolyze inositol 2-phosphate (I-2-P) and glucose-6-phosphate (G-6-P) in vitro, but not fructose-6-phosphate (F-6-P) and trehalose-6-phosphate (T-6-P).<ref>PMID:16325768</ref> <ref>PMID:18454554</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In many organisms, 3'-phosphoadenosine 5'-phosphate (PAP) is a product of two reactions in the sulfur activation pathway. The sulfurylation of biomolecules, catalyzed by sulfotransferases, uses 3'-phosphoadenosine 5'-phosphosulfate (PAPS) as a sulfate donor, producing the sulfated biomolecule and PAP product. Additionally, the first step in sulfate reduction for many bacteria and fungi reduces the sulfate moiety of PAPS, producing PAP and sulfite, which is subsequently reduced to sulfide. PAP is removed by the phosphatase activity of CysQ, a 3',5'-bisphosphate nucleotidase, yielding AMP and phosphate. Because excess PAP alters the equilibrium of the sulfur pathway and inhibits sulfotransferases, PAP concentrations can affect the levels of sulfur-containing metabolites. Therefore, CysQ, a divalent cation metal-dependent phosphatase, is a major regulator of this pathway. CysQ (Rv2131c) from Mycobacterium tuberculosis (Mtb) was successfully expressed, purified, and crystallized in a variety of ligand-bound states. Here we report six crystal structures of Mtb CysQ, including a ligand-free structure, a lithium-inhibited state with substrate PAP bound, and a product-bound complex with AMP, phosphate, and three Mg(2+) ions bound. Comparison of these structures together with homologues of the superfamily has provided insight into substrate specificity, metal coordination, and catalytic mechanism. | |||
Crystal Structures of Mycobacterium tuberculosis CysQ, with Substrate and Products Bound.,Erickson AI, Sarsam RD, Fisher AJ Biochemistry. 2015 Nov 17;54(45):6830-41. doi: 10.1021/acs.biochem.5b01000. Epub , 2015 Nov 5. PMID:26512869<ref>PMID:26512869</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5djh" style="background-color:#fffaf0;"></div> | ||
[[Category: Erickson | |||
==See Also== | |||
*[[Fructose-1%2C6-bisphosphatase 3D structures|Fructose-1%2C6-bisphosphatase 3D structures]] | |||
*[[Inositol monophosphatase 3D structures|Inositol monophosphatase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mycobacterium tuberculosis]] | |||
[[Category: Erickson AI]] | |||
[[Category: Fisher AJ]] | |||
Latest revision as of 00:44, 29 June 2023
Structure of M. tuberculosis CysQ, a PAP phosphatase with AMP, PO4, and 3Mg boundStructure of M. tuberculosis CysQ, a PAP phosphatase with AMP, PO4, and 3Mg bound
Structural highlights
FunctionCYSQ_MYCTU Phosphatase with a broad specificity. Its primary physiological function is to dephosphorylate 3'-phosphoadenosine 5'-phosphate (PAP) and 3'-phosphoadenosine 5'-phosphosulfate (PAPS). Thus, plays a role in mycobacterial sulfur metabolism, since it can serve as a key regulator of the sulfate assimilation pathway by controlling the pools of PAP and PAPS in the cell. To a lesser extent, is also able to hydrolyze inositol 1-phosphate (I-1-P), fructose 1,6-bisphosphate (FBP) (to fructose 6-phosphate (F-6-P)) and AMP in vitro, but this might not be significant in vivo. Glucose-1-phosphate (G-1-P), p-nitrophenyl phosphate (pNPP), and beta-glycerol phosphate (beta-GP) are also good substrates, compared to I-1-P. With much lower efficiency, can also hydrolyze inositol 2-phosphate (I-2-P) and glucose-6-phosphate (G-6-P) in vitro, but not fructose-6-phosphate (F-6-P) and trehalose-6-phosphate (T-6-P).[1] [2] Publication Abstract from PubMedIn many organisms, 3'-phosphoadenosine 5'-phosphate (PAP) is a product of two reactions in the sulfur activation pathway. The sulfurylation of biomolecules, catalyzed by sulfotransferases, uses 3'-phosphoadenosine 5'-phosphosulfate (PAPS) as a sulfate donor, producing the sulfated biomolecule and PAP product. Additionally, the first step in sulfate reduction for many bacteria and fungi reduces the sulfate moiety of PAPS, producing PAP and sulfite, which is subsequently reduced to sulfide. PAP is removed by the phosphatase activity of CysQ, a 3',5'-bisphosphate nucleotidase, yielding AMP and phosphate. Because excess PAP alters the equilibrium of the sulfur pathway and inhibits sulfotransferases, PAP concentrations can affect the levels of sulfur-containing metabolites. Therefore, CysQ, a divalent cation metal-dependent phosphatase, is a major regulator of this pathway. CysQ (Rv2131c) from Mycobacterium tuberculosis (Mtb) was successfully expressed, purified, and crystallized in a variety of ligand-bound states. Here we report six crystal structures of Mtb CysQ, including a ligand-free structure, a lithium-inhibited state with substrate PAP bound, and a product-bound complex with AMP, phosphate, and three Mg(2+) ions bound. Comparison of these structures together with homologues of the superfamily has provided insight into substrate specificity, metal coordination, and catalytic mechanism. Crystal Structures of Mycobacterium tuberculosis CysQ, with Substrate and Products Bound.,Erickson AI, Sarsam RD, Fisher AJ Biochemistry. 2015 Nov 17;54(45):6830-41. doi: 10.1021/acs.biochem.5b01000. Epub , 2015 Nov 5. PMID:26512869[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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