4acf: Difference between revisions
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==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.== | ==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]] 2.00Å' scene=''> | <StructureSection load='4acf' size='340' side='right' caption='[[4acf]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4acf]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <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> | ||
</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='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> | ||
<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='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='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='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'>[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://www.rcsb.org/pdb/explore.do?structureId=4acf RCSB], [http://www.ebi.ac.uk/pdbsum/4acf PDBsum]</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> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4acf" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Glutamate--ammonia ligase]] | [[Category: Glutamate--ammonia ligase]] | ||
[[Category: | [[Category: Myctu]] | ||
[[Category: Mowbray, S L]] | [[Category: Mowbray, S L]] | ||
[[Category: Nilsson, M T]] | [[Category: Nilsson, M T]] | ||
Revision as of 22:13, 10 December 2016
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.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.
Structural highlights
Publication Abstract from PubMedGlutamine 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References |
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