1htq

From Proteopedia

(Difference between revisions)

Current revision

Multicopy crystallographic structure of a relaxed glutamine synthetase from Mycobacterium tuberculosis

Structural highlights

1htq is a 24 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4Å, 10 models
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GLN1B_MYCTU Involved in nitrogen metabolism via ammonium assimilation. Catalyzes the ATP-dependent biosynthesis of glutamine from glutamate and ammonia (PubMed:12819079, PubMed:7937767). Also able to use GTP (PubMed:7937767). D-glutamate is a poor substrate, and DL-glutamate shows about 50% of the standard specific activity (PubMed:7937767). Also plays a key role in controlling the ammonia levels within infected host cells and so contributes to the pathogens capacity to inhibit phagosome acidification and phagosome-lysosome fusion (PubMed:12819079, PubMed:7937767). Involved in cell wall biosynthesis via the production of the major component poly-L-glutamine (PLG) (PubMed:10618433, PubMed:7937767). PLG synthesis in the cell wall occurs only in nitrogen limiting conditions and on the contrary high nitrogen conditions inhibit PLG synthesis (Probable).^[1] ^[2] ^[3] ^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The crystal structure of glutamine synthetase (GS) from Mycobacterium tuberculosis determined at 2.4 A resolution reveals citrate and AMP bound in the active site. The structure was refined with strict 24-fold noncrystallographic symmetry (NCS) constraints and has an R-factor of 22.7% and an R-free of 25.5%. Multicopy refinement using 10 atomic models and strict 24-fold NCS constraints further reduced the R-factor to 20.4% and the R-free to 23.2%. The multicopy model demonstrates the range of atomic displacements of catalytic and regulatory loops in glutamine synthesis, simulating loop motions. A comparison with loop positions in substrate complexes of GS from Salmonella typhimurium shows that the Asp50 and Glu327 loops close over the active site during catalysis. These loop closures are preceded by a conformational change of the Glu209 beta-strand upon metal ion or ATP binding that converts the enzyme from a relaxed to a taut state. We propose a model of the GS regulatory mechanism based on the loop motions in which adenylylation of the Tyr397 loop reverses the effect of metal ion binding, and regulates intermediate formation by preventing closure of the Glu327 loop.

Multicopy crystallographic refinement of a relaxed glutamine synthetase from Mycobacterium tuberculosis highlights flexible loops in the enzymatic mechanism and its regulation.,Gill HS, Pfluegl GM, Eisenberg D Biochemistry. 2002 Aug 6;41(31):9863-72. PMID:12146952^[5]

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

References

↑ Harth G, Zamecnik PC, Tang JY, Tabatadze D, Horwitz MA. Treatment of Mycobacterium tuberculosis with antisense oligonucleotides to glutamine synthetase mRNA inhibits glutamine synthetase activity, formation of the poly-L-glutamate/glutamine cell wall structure, and bacterial replication. Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):418-23. PMID:10618433 doi:10.1073/pnas.97.1.418
↑ Tullius MV, Harth G, Horwitz MA. Glutamine synthetase GlnA1 is essential for growth of Mycobacterium tuberculosis in human THP-1 macrophages and guinea pigs. Infect Immun. 2003 Jul;71(7):3927-36. PMID:12819079 doi:10.1128/IAI.71.7.3927-3936.2003
↑ Harth G, Clemens DL, Horwitz MA. Glutamine synthetase of Mycobacterium tuberculosis: extracellular release and characterization of its enzymatic activity. Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9342-6. PMID:7937767 doi:10.1073/pnas.91.20.9342
↑ Harth G, Horwitz MA. Expression and efficient export of enzymatically active Mycobacterium tuberculosis glutamine synthetase in Mycobacterium smegmatis and evidence that the information for export is contained within the protein. J Biol Chem. 1997 Sep 5;272(36):22728-35. PMID:9278431 doi:10.1074/jbc.272.36.22728
↑ Gill HS, Pfluegl GM, Eisenberg D. Multicopy crystallographic refinement of a relaxed glutamine synthetase from Mycobacterium tuberculosis highlights flexible loops in the enzymatic mechanism and its regulation. Biochemistry. 2002 Aug 6;41(31):9863-72. PMID:12146952

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1htq"

Categories: Large Structures | Mycobacterium tuberculosis | Eisenberg D | Gill HS | Pfluegl GM

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1htq]] is a 24 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=1HTQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HTQ 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]] 2.4&#8491;</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]] 2.4&#8491;, 10 models</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=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=1htq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1htq OCA], [https://pdbe.org/1htq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1htq RCSB], [https://www.ebi.ac.uk/pdbsum/1htq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1htq ProSAT]</span></td></tr>
 </table>
 == Function ==
-[https://www.uniprot.org/uniprot/GLN1B_MYCTU GLN1B_MYCTU] Involved in nitrogen metabolism via ammonium assimilation. Catalyzes the ATP-dependent biosynthesis of glutamine from glutamate and ammonia (PubMed:7937767, PubMed:12819079). Also able to use GTP (PubMed:7937767). D-glutamate is a poor substrate, and DL-glutamate shows about 50% of the standard specific activity (PubMed:7937767). Also plays a key role in controlling the ammonia levels within infected host cells and so contributes to the pathogens capacity to inhibit phagosome acidification and phagosome-lysosome fusion (PubMed:7937767, PubMed:12819079). Involved in cell wall biosynthesis via the production of the major component poly-L-glutamine (PLG) (PubMed:7937767, PubMed:10618433). PLG synthesis in the cell wall occurs only in nitrogen limiting conditions and on the contrary high nitrogen conditions inhibit PLG synthesis (Probable).<ref>PMID:10618433</ref> <ref>PMID:12819079</ref> <ref>PMID:7937767</ref> <ref>PMID:9278431</ref>
+[https://www.uniprot.org/uniprot/GLN1B_MYCTU GLN1B_MYCTU] Involved in nitrogen metabolism via ammonium assimilation. Catalyzes the ATP-dependent biosynthesis of glutamine from glutamate and ammonia (PubMed:12819079, PubMed:7937767). Also able to use GTP (PubMed:7937767). D-glutamate is a poor substrate, and DL-glutamate shows about 50% of the standard specific activity (PubMed:7937767). Also plays a key role in controlling the ammonia levels within infected host cells and so contributes to the pathogens capacity to inhibit phagosome acidification and phagosome-lysosome fusion (PubMed:12819079, PubMed:7937767). Involved in cell wall biosynthesis via the production of the major component poly-L-glutamine (PLG) (PubMed:10618433, PubMed:7937767). PLG synthesis in the cell wall occurs only in nitrogen limiting conditions and on the contrary high nitrogen conditions inhibit PLG synthesis (Probable).<ref>PMID:10618433</ref> <ref>PMID:12819079</ref> <ref>PMID:7937767</ref> <ref>PMID:9278431</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

1htq

From Proteopedia

Current revision

Multicopy crystallographic structure of a relaxed glutamine synthetase from Mycobacterium tuberculosis

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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