4acf: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 ==CRYSTAL STRUCTURE OF MYCOBACTERIUM TUBERCULOSIS GLUTAMINE SYNTHETASE IN COMPLEX WITH IMIDAZOPYRIDINE INHIBITOR ((4-(6-BROMO-3-(BUTYLAMINO)IMIDAZO(1,2-A)PYRIDIN-2-YL)PHENOXY) ACETIC ACID) AND L-METHIONINE-S-SULFOXIMINE PHOSPHATE.==
-<StructureSection load='4acf' size='340' side='right' caption='[[4acf]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='4acf' size='340' side='right'caption='[[4acf]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4acf]] is a 6 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=4ACF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ACF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4acf]] is a 6 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=4ACF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ACF FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=46B:{4-[6-BROMO-3-(BUTYLAMINO)IMIDAZO[1,2-A]PYRIDIN-2-YL]PHENOXY}ACETIC+ACID'>46B</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=P3S:L-METHIONINE-S-SULFOXIMINE+PHOSPHATE'>P3S</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1hto|1hto]], [[1htq|1htq]], [[3zxr|3zxr]], [[2whi|2whi]], [[2bvc|2bvc]], [[2wgs|2wgs]], [[3zxv|3zxv]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=46B:{4-[6-BROMO-3-(BUTYLAMINO)IMIDAZO[1,2-A]PYRIDIN-2-YL]PHENOXY}ACETIC+ACID'>46B</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=P3S:L-METHIONINE-S-SULFOXIMINE+PHOSPHATE'>P3S</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glutamate--ammonia_ligase Glutamate--ammonia ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.1.2 6.3.1.2] </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=4acf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4acf OCA], [https://pdbe.org/4acf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4acf RCSB], [https://www.ebi.ac.uk/pdbsum/4acf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4acf 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=4acf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4acf OCA], [http://pdbe.org/4acf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4acf RCSB], [http://www.ebi.ac.uk/pdbsum/4acf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4acf ProSAT]</span></td></tr>
 </table>
-<div style="background-color:#fffaf0;">
+== Function ==
-== Publication Abstract from PubMed ==
+[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>
-Glutamine synthetase catalyzes the ligation of glutamate and ammonia to form glutamine, with the resulting hydrolysis of ATP. The enzyme is a central component of bacterial nitrogen metabolism and is a potential drug target. Here, we report a high-yield recombinant expression system for glutamine synthetase of Mycobacterium tuberculosis together with a simple purification. The procedure allowed the structure of a complex with a phosphorylated form of the inhibitor methionine sulfoximine, magnesium, and ADP to be solved by molecular replacement and refined at 2.1-A resolution. To our knowledge, this study provides the first reported structure for a taut form of the M. tuberculosis enzyme, similar to that observed for the Salmonella enzyme earlier. The phospho compound, generated in situ by an active enzyme, mimics the phosphorylated tetrahedral adduct at the transition state. Some differences in ligand interactions of the protein with both phosphorylated compound and nucleotide are observed compared with earlier structures; a third metal ion also is found. The importance of these differences in the catalytic mechanism is discussed; the results will help guide the search for specific inhibitors of potential therapeutic interest.
-Structure of Mycobacterium tuberculosis glutamine synthetase in complex with a transition-state mimic provides functional insights.,Krajewski WW, Jones TA, Mowbray SL Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10499-504. Epub 2005 Jul 18. PMID:16027359<ref>PMID:16027359</ref>
+==See Also==
+*[[Glutamine synthetase 3D structures|Glutamine synthetase 3D structures]]
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 4acf" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Glutamate--ammonia ligase]]
+[[Category: Large Structures]]
-[[Category: Myctu]]
+[[Category: Mycobacterium tuberculosis H37Rv]]
-[[Category: Mowbray, S L]]
+[[Category: Mowbray SL]]
-[[Category: Nilsson, M T]]
+[[Category: Nilsson MT]]
-[[Category: Glna1]]
-[[Category: Ligase]]
-[[Category: Mt2278]]
-[[Category: Nucleotide-binding]]
-[[Category: Rv2220]]
-[[Category: Synthetase]]
-[[Category: Taut state]]
-[[Category: Tri-substituted imidazole]]