Sandbox Reserved 992: Difference between revisions

Class C β-lactamases share a very similar mechanism as the Class A β-lactams, acylation followed by hydrolytic deacylation.4 Class C differs from A in that the hydrolytic water, activated by tyrosine 150, approaches the enzyme from the opposite side. This activated water is what allows β-lactamases to deacylation and maintain their catalytic function, while PBPs cannot.<ref name="Bush 2013" /> Class D differs from A and C in that it has an N-carboxylated active site lysine which hydrogen bonds with the active site serine.<ref>Mobashery, Shahriar. Bacterial Resistance to β-Lactam Antibiotics:  Compelling Opportunism, Compelling Opportunity. Chem. Rev. (2005) 105, 395-424.</ref>

Class C β-lactamases, among many other enzyme types, also contain a structural component known as an [http://en.m.wikipedia.org/wiki/Oxyanion_hole oxyanion hole]. This pocket of [http://en.m.wikipedia.org/wiki/Hydrophile hydrophilic] residues directly stabilizes the high-energy [http://en.m.wikipedia.org/wiki/Tetrahedral_carbonyl_addition_compound tetrahedral intermediate], lowering the [http://en.m.wikipedia.org/wiki/Activation_energy activation energy] and promoting a faster overall reaction.<ref>Albert Lehninger et al. (2008). Principles of Biochemistry (5th ed.). Macmillan. p. 207.</ref><ref>Livermore, David. β-Lactamase mediated resistance and opportunities for its control. J. Antimicrob. Chemother. (1998) 41 (suppl 4): 25-41.</ref> The hydrophobicity of <scene name='69/691534/Hydrophobicity_in_adc-1/1'>ADC-1</scene><ref>Bhattacharya, M.,  Toth, M.,  Antunes, N.T.,  Smith, C.A.,  Vakulenko, S.B. Structure of the extended-spectrum class C β-lactamase ADC-1 from Acinetobacter baumannii. Acta Crystallogr. (2014),Sect.D 70: 760-771</ref>, a class C β-lactamase, is shown here.  

== Clinical Significance ==