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01000naa a22002652 4500 |
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NLM121837661 |
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DE-627 |
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20231222193934.0 |
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tu |
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231222s2002 xx ||||| 00| ||eng c |
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|a pubmed24n0406.xml
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|a (DE-627)NLM121837661
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|a (NLM)12395425
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|a DE-627
|b ger
|c DE-627
|e rakwb
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| 041 |
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|a eng
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| 100 |
1 |
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|a Massova, Irina
|e verfasserin
|4 aut
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| 245 |
1 |
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|a pKa, MM, and QM studies of mechanisms of beta-lactamases and penicillin-binding proteins
|b acylation step
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| 264 |
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1 |
|c 2002
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| 336 |
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|a Text
|b txt
|2 rdacontent
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| 337 |
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|a ohne Hilfsmittel zu benutzen
|b n
|2 rdamedia
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| 338 |
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|a Band
|b nc
|2 rdacarrier
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| 500 |
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|a Date Completed 13.12.2002
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| 500 |
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|a Date Revised 14.11.2007
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| 500 |
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|a published: Print
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|a Citation Status MEDLINE
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| 520 |
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|a Copyright 2002 Wiley Periodicals, Inc.
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| 520 |
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|a The acylation step of the catalytic mechanism of beta-lactamases and penicillin-binding proteins (PBPs) has been studied with various approaches. The methods applied range from molecular dynamics (MD) simulations to multiple titration calculations using the Poisson-Boltzmann approach to quantum mechanical (QM) methods. The mechanism of class A beta-lactamases was investigated in the greatest detail. Most approaches support the critical role of Glu-166 and hydrolytic water in the acylation step of the enzymatic catalysis in class A beta-lactamases. The details of the catalytic mechanism have been revealed by the QM approach, which clearly pointed out the critical role of Glu-166 acting as a general base in the acylation step with preferred substrates. Lys-73 shuffles a proton abstracted by Glu-166 O(epsilon ) to the beta-lactam nitrogen through Ser-130 hydroxyl. This proton is transferred from O(gamma) of the catalytic Ser-70 through the bridging hydrolytic water to Glu-166 O(epsilon ). Then the hydrogen is simultaneously passed through S(N)2 inversion mechanism at Lys-73 N(zeta) to Ser-130 O(gamma), which loses its proton to the beta-lactam nitrogen. The protonation of beta-lactam nitrogen proceeds with an immediate ring opening and collapse of the first tetrahedral species into an acyl-enzyme intermediate. However, the studies that considered the effect of solvation lower the barrier for the pathway, which utilizes Lys-73 as a general base, thus creating a possibility of multiple mechanisms for the acylation step in the class A beta-lactamases. These findings help explain the exceptional efficiency of these enzymes. They emphasize an important role of Glu-166, Lys-73, and Ser-130 for enzymatic catalysis and shed light on details of the acylation step of class A beta-lactamase mechanism. The acylation step for class C beta-lactamases and six classes of PBPs were also considered with continuum solvent models and MD simulations
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| 650 |
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4 |
|a Journal Article
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| 650 |
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4 |
|a Research Support, U.S. Gov't, P.H.S.
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| 650 |
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7 |
|a Bacterial Proteins
|2 NLM
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| 650 |
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7 |
|a Carrier Proteins
|2 NLM
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| 650 |
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7 |
|a Penicillin-Binding Proteins
|2 NLM
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| 650 |
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7 |
|a Protons
|2 NLM
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| 650 |
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7 |
|a Solvents
|2 NLM
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| 650 |
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7 |
|a Peptidyl Transferases
|2 NLM
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| 650 |
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7 |
|a EC 2.3.2.12
|2 NLM
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| 650 |
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7 |
|a Hexosyltransferases
|2 NLM
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| 650 |
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7 |
|a EC 2.4.1.-
|2 NLM
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| 650 |
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7 |
|a Muramoylpentapeptide Carboxypeptidase
|2 NLM
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| 650 |
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7 |
|a EC 3.4.17.8
|2 NLM
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| 650 |
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7 |
|a beta-Lactamases
|2 NLM
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| 650 |
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7 |
|a EC 3.5.2.6
|2 NLM
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| 700 |
1 |
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|a Kollman, Peter A
|e verfasserin
|4 aut
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| 773 |
0 |
8 |
|i Enthalten in
|t Journal of computational chemistry
|d 1984
|g 23(2002), 16 vom: 01. Dez., Seite 1559-76
|w (DE-627)NLM098138448
|x 1096-987X
|7 nnns
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| 773 |
1 |
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|g volume:23
|g year:2002
|g number:16
|g day:01
|g month:12
|g pages:1559-76
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| 912 |
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|a GBV_USEFLAG_A
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| 912 |
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|a SYSFLAG_A
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| 912 |
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|a GBV_NLM
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| 912 |
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|a GBV_ILN_350
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| 951 |
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|a AR
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| 952 |
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|d 23
|j 2002
|e 16
|b 01
|c 12
|h 1559-76
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