3V50

Complex of SHV S130G mutant beta-lactamase complexed to SA2-13

3V50 の概要

• エントリーDOI: 10.2210/pdb3v50/pdb
• 関連するPDBエントリー: 2H10 2H5S 3OPP 3OPR
• 分子名称: Beta-lactamase, (3R)-4-[(4-CARBOXYBUTANOYL)OXY]-N-[(1E)-3-OXOPROP-1-EN-1-YL]-3-SULFINO-D-VALINE, CYCLOHEXYL-HEXYL-BETA-D-MALTOSIDE, ... (4 entities in total)
• 機能のキーワード: class a beta-lactamase fold, hydrolyze b-lactam antibiotics, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Klebsiella pneumoniae
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 30259.55

構造登録者

Wei, K.,van den Akker, F. (登録日: 2011-12-15, 公開日: 2012-08-08)

主引用文献

Ke, W.,Rodkey, E.A.,Sampson, J.M.,Skalweit, M.J.,Sheri, A.,Pagadala, S.R.,Nottingham, M.D.,Buynak, J.D.,Bonomo, R.A.,van den Akker, F.
The importance of the trans-enamine intermediate as a beta-lactamase inhibition strategy probed in inhibitor-resistant SHV beta-lactamase variants.
Chemmedchem, 7:1002-1008, 2012

PubMed Abstract: The ability of bacteria to express inhibitor-resistant (IR) β-lactamases is stimulating the development of novel inhibitors of these enzymes. The 2'β-glutaroxypenicillinate sulfone, SA2-13, was previously designed to enhance the stabilization of the deacylation-refractory, trans-enamine inhibitory intermediate. To test whether this mode of inhibition can overcome different IR mutations, we determined the binding mode of SA2-13 through X-ray crystallography, obtaining co-crystals of the inhibitor-protein complex by soaking crystals of the IR sulfhydryl variable (SHV) β-lactamase variants S130G and M69V with the inhibitor. The 1.45 Å crystal structure of the S130G SHV:SA2-13 complex reveals that SA2-13 is still able to form the stable trans-enamine intermediate similar to the wild-type complex structure, yet with its carboxyl linker shifted deeper into the active site in the space vacated by the S130G mutation. In contrast, data from crystals of the M69V SHV:SA2-13 complex at 1.3 Å did not reveal clear inhibitor density indicating that this IR variant disfavors the trans-enamine conformation, likely due to a subtle shift in A237.

PubMed: 22438274
DOI: 10.1002/cmdc.201200006

実験手法

X-RAY DIFFRACTION (1.45 Å)