2ffy
From Proteopedia
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|PDB= 2ffy |SIZE=350|CAPTION= <scene name='initialview01'>2ffy</scene>, resolution 1.07Å | |PDB= 2ffy |SIZE=350|CAPTION= <scene name='initialview01'>2ffy</scene>, resolution 1.07Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SM3:(1R)-1-(2-THIENYLACETYLAMINO)-1-PHENYLMETHYLBORONIC+ACID'>SM3</scene> |
| - | |ACTIVITY= [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] | + | |ACTIVITY= <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> |
|GENE= ampC, ampA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli]) | |GENE= ampC, ampA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1pi4|1PI4]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ffy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ffy OCA], [http://www.ebi.ac.uk/pdbsum/2ffy PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2ffy RCSB]</span> | ||
}} | }} | ||
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[[Category: Roth, T A.]] | [[Category: Roth, T A.]] | ||
[[Category: Shoichet, B K.]] | [[Category: Shoichet, B K.]] | ||
| - | [[Category: | + | [[Category: ampc]] |
| - | [[Category: | + | [[Category: beta-lactamase]] |
| - | [[Category: | + | [[Category: boronic acid]] |
| - | [[Category: | + | [[Category: deacylation]] |
| + | [[Category: transition state]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:02:15 2008'' |
Revision as of 00:02, 31 March 2008
| |||||||
| , resolution 1.07Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Gene: | ampC, ampA (Escherichia coli) | ||||||
| Activity: | Beta-lactamase, with EC number 3.5.2.6 | ||||||
| Related: | 1PI4
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
AmpC beta-lactamase N289A mutant in complex with a boronic acid deacylation transition state analog compound SM3
Overview
Beta-lactamases confer bacterial resistance to beta-lactam antibiotics, such as penicillins. The characteristic class C beta-lactamase AmpC catalyzes the reaction with several key residues including Ser64, Tyr150, and Lys67. Here, we describe a 1.07 A X-ray crystallographic structure of AmpC beta-lactamase in complex with a boronic acid deacylation transition-state analogue. The high quality of the electron density map allows the determination of many proton positions. The proton on the Tyr150 hydroxyl group is clearly visible and is donated to the boronic oxygen mimicking the deacylation water. Meanwhile, Lys67 hydrogen bonds with Ser64Ogamma, Asn152Odelta1, and the backbone oxygen of Ala220. This suggests that this residue is positively charged and has relinquished the hydrogen bond with Tyr150 observed in acyl-enzyme complex structures. Together with previous biochemical and NMR studies, these observations indicate that Tyr150 is protonated throughout the reaction coordinate, disfavoring mechanisms that involve a stable tyrosinate as the general base for deacylation. Rather, the hydroxyl of Tyr150 appears to be well positioned to electrostatically stabilize the negative charge buildup in the tetrahedral high-energy intermediate. This structure, in itself, appears consistent with a mechanism involving either Tyr150 acting as a transient catalytic base in conjunction with a neutral Lys67 or the lactam nitrogen as the general base. Whereas mutagenesis studies suggest that Lys67 may be replaced by an arginine, disfavoring the conjugate base mechanism, distinguishing between these two hypotheses may ultimately depend on direct determination of the pK(a) of Lys67 along the reaction coordinate.
About this Structure
2FFY is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
The deacylation mechanism of AmpC beta-lactamase at ultrahigh resolution., Chen Y, Minasov G, Roth TA, Prati F, Shoichet BK, J Am Chem Soc. 2006 Mar 8;128(9):2970-6. PMID:16506777
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