4wio

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the C89A GMP synthetase inactive mutant from Plasmodium falciparum in complex with glutamine

Structural highlights

4wio is a 1 chain structure with sequence from Plasmodium falciparum 3D7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.15Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GUAA_PLAF7 Catalyzes the conversion of xanthine monophosphate (XMP) to GMP in the presence of glutamine and ATP through an adenyl-XMP intermediate, which is the final step of de novo synthesis of GMP (PubMed:17868038, PubMed:21413787, PubMed:26592566, PubMed:32358899). The conversion of XMP to GMP involves the coordinated action of the glutamine amidotransferase (GATase) domain that catalyzes the hydrolysis of the amide side chain of glutamine producing ammonia and the ATP pyrophosphatase (ATPPase) domain that catalyzes the synthesis of adenyl-XMP intermediate from ATP (PubMed:17868038, PubMed:21413787, PubMed:26592566, PubMed:32358899). The ammonia produced by the GATase domain is tunnelled to the ATP-PPase domain where it attacks the adenyl-XMP intermediate generating GMP (PubMed:17868038, PubMed:21413787, PubMed:26592566, PubMed:32358899).^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

GMP synthetase (GMPS), a key enzyme in the purine biosynthetic pathway performs catalysis through a coordinated process across two catalytic pockets for which the mechanism remains unclear. Crystal structures of Plasmodium falciparum GMPS in conjunction with mutational and enzyme kinetic studies reported here provide evidence that an 85 degrees rotation of the GATase domain is required for ammonia channelling and thus for the catalytic activity of this two-domain enzyme. We suggest that conformational changes in helix 371-375 holding catalytic residues and in loop 376-401 along the rotation trajectory trigger the different steps of catalysis, and establish the central role of Glu374 in allostery and inter-domain crosstalk. These studies reveal the mechanism of domain rotation and inter-domain communication, providing a molecular framework for the function of all single polypeptide GMPSs and form a solid basis for rational drug design targeting this therapeutically important enzyme.

Active site coupling in Plasmodium falciparum GMP synthetase is triggered by domain rotation.,Ballut L, Violot S, Shivakumaraswamy S, Thota LP, Sathya M, Kunala J, Dijkstra BW, Terreux R, Haser R, Balaram H, Aghajari N Nat Commun. 2015 Nov 23;6:8930. doi: 10.1038/ncomms9930. PMID:26592566^[5]

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

References

↑ Bhat JY, Shastri BG, Balaram H. Kinetic and biochemical characterization of Plasmodium falciparum GMP synthetase. Biochem J. 2008 Jan 1;409(1):263-73. PMID:17868038 doi:10.1042/BJ20070996
↑ Bhat JY, Venkatachala R, Singh K, Gupta K, Sarma SP, Balaram H. Ammonia channeling in Plasmodium falciparum GMP synthetase: investigation by NMR spectroscopy and biochemical assays. Biochemistry. 2011 Apr 26;50(16):3346-56. PMID:21413787 doi:10.1021/bi1017057
↑ Ballut L, Violot S, Shivakumaraswamy S, Thota LP, Sathya M, Kunala J, Dijkstra BW, Terreux R, Haser R, Balaram H, Aghajari N. Active site coupling in Plasmodium falciparum GMP synthetase is triggered by domain rotation. Nat Commun. 2015 Nov 23;6:8930. doi: 10.1038/ncomms9930. PMID:26592566 doi:http://dx.doi.org/10.1038/ncomms9930
↑ Shivakumaraswamy S, Pandey N, Ballut L, Violot S, Aghajari N, Balaram H. Helices on Interdomain Interface Couple Catalysis in the ATPPase Domain with Allostery in Plasmodium falciparum GMP Synthetase. Chembiochem. 2020 Oct 1;21(19):2805-2817. PMID:32358899 doi:10.1002/cbic.202000158
↑ Ballut L, Violot S, Shivakumaraswamy S, Thota LP, Sathya M, Kunala J, Dijkstra BW, Terreux R, Haser R, Balaram H, Aghajari N. Active site coupling in Plasmodium falciparum GMP synthetase is triggered by domain rotation. Nat Commun. 2015 Nov 23;6:8930. doi: 10.1038/ncomms9930. PMID:26592566 doi:http://dx.doi.org/10.1038/ncomms9930

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 1: / Line 1: @@
 ==Crystal structure of the C89A GMP synthetase inactive mutant from Plasmodium falciparum in complex with glutamine==
-<StructureSection load='4wio' size='340' side='right' caption='[[4wio]], [[Resolution|resolution]] 3.15&Aring;' scene=''>
+<StructureSection load='4wio' size='340' side='right'caption='[[4wio]], [[Resolution|resolution]] 3.15&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4wio]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WIO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WIO FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4wio]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WIO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WIO FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GLN:GLUTAMINE'>GLN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.15&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4wim|4wim]], [[4win|4win]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLN:GLUTAMINE'>GLN</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/GMP_synthase_(glutamine-hydrolyzing) GMP synthase (glutamine-hydrolyzing)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.5.2 6.3.5.2] </span></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=4wio FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wio OCA], [https://pdbe.org/4wio PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wio RCSB], [https://www.ebi.ac.uk/pdbsum/4wio PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wio ProSAT]</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=4wio FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wio OCA], [http://pdbe.org/4wio PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4wio RCSB], [http://www.ebi.ac.uk/pdbsum/4wio PDBsum]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/GUAA_PLAF7 GUAA_PLAF7] Catalyzes the conversion of xanthine monophosphate (XMP) to GMP in the presence of glutamine and ATP through an adenyl-XMP intermediate, which is the final step of de novo synthesis of GMP (PubMed:17868038, PubMed:21413787, PubMed:26592566, PubMed:32358899). The conversion of XMP to GMP involves the coordinated action of the glutamine amidotransferase (GATase) domain that catalyzes the hydrolysis of the amide side chain of glutamine producing ammonia and the ATP pyrophosphatase (ATPPase) domain that catalyzes the synthesis of adenyl-XMP intermediate from ATP (PubMed:17868038, PubMed:21413787, PubMed:26592566, PubMed:32358899). The ammonia produced by the GATase domain is tunnelled to the ATP-PPase domain where it attacks the adenyl-XMP intermediate generating GMP (PubMed:17868038, PubMed:21413787, PubMed:26592566, PubMed:32358899).<ref>PMID:17868038</ref> <ref>PMID:21413787</ref> <ref>PMID:26592566</ref> <ref>PMID:32358899</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 21: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Aghajari, N]]
+[[Category: Large Structures]]
-[[Category: Ballut, L]]
+[[Category: Plasmodium falciparum 3D7]]
-[[Category: Haser, R]]
+[[Category: Aghajari N]]
-[[Category: Violot, S]]
+[[Category: Ballut L]]
-[[Category: Gmp synthetase]]
+[[Category: Haser R]]
-[[Category: Ligase]]
+[[Category: Violot S]]
-[[Category: Purine salvage pathway]]

4wio

From Proteopedia

Current revision

Crystal structure of the C89A GMP synthetase inactive mutant from Plasmodium falciparum in complex with glutamine

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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