6b68: Difference between revisions
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==Beta-Lactamase, 100ms timepoint, mixed, shards crystal form== | |||
<StructureSection load='6b68' size='340' side='right' caption='[[6b68]], [[Resolution|resolution]] 2.15Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6b68]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B68 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B68 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9F2:Ceftriaxone'>9F2</scene>, <scene name='pdbligand=FZS:(2R)-2-[(1S)-1-{[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl]amino}-2-hydroxyethyl]-5-methylidene-5,6-dihydro-2H-1,3-thiazine-4-carboxylic+acid'>FZS</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">[[6b5x|6b5x]]</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </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=6b68 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b68 OCA], [http://pdbe.org/6b68 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b68 RCSB], [http://www.ebi.ac.uk/pdbsum/6b68 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b68 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
BACKGROUND: Ever since the first atomic structure of an enzyme was solved, the discovery of the mechanism and dynamics of reactions catalyzed by biomolecules has been the key goal for the understanding of the molecular processes that drive life on earth. Despite a large number of successful methods for trapping reaction intermediates, the direct observation of an ongoing reaction has been possible only in rare and exceptional cases. RESULTS: Here, we demonstrate a general method for capturing enzyme catalysis "in action" by mix-and-inject serial crystallography (MISC). Specifically, we follow the catalytic reaction of the Mycobacterium tuberculosis beta-lactamase with the third-generation antibiotic ceftriaxone by time-resolved serial femtosecond crystallography. The results reveal, in near atomic detail, antibiotic cleavage and inactivation from 30 ms to 2 s. CONCLUSIONS: MISC is a versatile and generally applicable method to investigate reactions of biological macromolecules, some of which are of immense biological significance and might be, in addition, important targets for structure-based drug design. With megahertz X-ray pulse rates expected at the Linac Coherent Light Source II and the European X-ray free-electron laser, multiple, finely spaced time delays can be collected rapidly, allowing a comprehensive description of biomolecular reactions in terms of structure and kinetics from the same set of X-ray data. | |||
Enzyme intermediates captured "on the fly" by mix-and-inject serial crystallography.,Olmos JL Jr, Pandey S, Martin-Garcia JM, Calvey G, Katz A, Knoska J, Kupitz C, Hunter MS, Liang M, Oberthuer D, Yefanov O, Wiedorn M, Heyman M, Holl M, Pande K, Barty A, Miller MD, Stern S, Roy-Chowdhury S, Coe J, Nagaratnam N, Zook J, Verburgt J, Norwood T, Poudyal I, Xu D, Koglin J, Seaberg MH, Zhao Y, Bajt S, Grant T, Mariani V, Nelson G, Subramanian G, Bae E, Fromme R, Fung R, Schwander P, Frank M, White TA, Weierstall U, Zatsepin N, Spence J, Fromme P, Chapman HN, Pollack L, Tremblay L, Ourmazd A, Phillips GN Jr, Schmidt M BMC Biol. 2018 May 31;16(1):59. doi: 10.1186/s12915-018-0524-5. PMID:29848358<ref>PMID:29848358</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6b68" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Beta-lactamase]] | |||
[[Category: Pandey, S]] | |||
[[Category: Schmidt, M]] | [[Category: Schmidt, M]] | ||
[[Category: | [[Category: Antibiotic]] | ||
[[Category: Hydrolase-antibiotic complex]] | |||
Revision as of 08:33, 27 June 2018
Beta-Lactamase, 100ms timepoint, mixed, shards crystal formBeta-Lactamase, 100ms timepoint, mixed, shards crystal form
Structural highlights
Publication Abstract from PubMedBACKGROUND: Ever since the first atomic structure of an enzyme was solved, the discovery of the mechanism and dynamics of reactions catalyzed by biomolecules has been the key goal for the understanding of the molecular processes that drive life on earth. Despite a large number of successful methods for trapping reaction intermediates, the direct observation of an ongoing reaction has been possible only in rare and exceptional cases. RESULTS: Here, we demonstrate a general method for capturing enzyme catalysis "in action" by mix-and-inject serial crystallography (MISC). Specifically, we follow the catalytic reaction of the Mycobacterium tuberculosis beta-lactamase with the third-generation antibiotic ceftriaxone by time-resolved serial femtosecond crystallography. The results reveal, in near atomic detail, antibiotic cleavage and inactivation from 30 ms to 2 s. CONCLUSIONS: MISC is a versatile and generally applicable method to investigate reactions of biological macromolecules, some of which are of immense biological significance and might be, in addition, important targets for structure-based drug design. With megahertz X-ray pulse rates expected at the Linac Coherent Light Source II and the European X-ray free-electron laser, multiple, finely spaced time delays can be collected rapidly, allowing a comprehensive description of biomolecular reactions in terms of structure and kinetics from the same set of X-ray data. Enzyme intermediates captured "on the fly" by mix-and-inject serial crystallography.,Olmos JL Jr, Pandey S, Martin-Garcia JM, Calvey G, Katz A, Knoska J, Kupitz C, Hunter MS, Liang M, Oberthuer D, Yefanov O, Wiedorn M, Heyman M, Holl M, Pande K, Barty A, Miller MD, Stern S, Roy-Chowdhury S, Coe J, Nagaratnam N, Zook J, Verburgt J, Norwood T, Poudyal I, Xu D, Koglin J, Seaberg MH, Zhao Y, Bajt S, Grant T, Mariani V, Nelson G, Subramanian G, Bae E, Fromme R, Fung R, Schwander P, Frank M, White TA, Weierstall U, Zatsepin N, Spence J, Fromme P, Chapman HN, Pollack L, Tremblay L, Ourmazd A, Phillips GN Jr, Schmidt M BMC Biol. 2018 May 31;16(1):59. doi: 10.1186/s12915-018-0524-5. PMID:29848358[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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