ELIZA

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286534 occurrences (No.87 in the rank) during 5 years in the PubMed. [cache]

362) Pre-steady-state kinetic analysis indicates that the rate-limiting step for OXA-48 and OXA-163 hydrolysis of carbapenems is deacylation and that the greatly reduced carbapenemase activity of OXA-163 compared to that of OXA-48 is due entirely to a slower deacylation reaction.

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PMID:33492952 DOI:10.1021/acsinfecdis.0c00798

2021 ACS infectious diseases

* Mechanistic Basis of OXA-48-like β-Lactamases' Hydrolysis of Carbapenems.

- Carbapenem-hydrolyzing class D β-lactamases (CHDLs) are an important source of resistance to these last resort β-lactam antibiotics. OXA-48 is a member of a group of CHDLs named OXA-48-like enzymes. On the basis of sequence similarity, OXA-163 can be classified as an OXA-48-like enzyme, but it has altered substrate specificity. Compared to OXA-48, it shows impaired activity for carbapenems but displays an enhanced hydrolysis of oxyimino-cephalosporins. Here, we address the mechanistic and structural basis for carbapenem hydrolysis by OXA-48-like enzymes. Pre-steady-state kinetic analysis indicates that the rate-limiting step for OXA-48 and OXA-163 hydrolysis of carbapenems is deacylation and that the greatly reduced carbapenemase activity of OXA-163 compared to that of OXA-48 is due entirely to a slower deacylation reaction. Furthermore, our structural data indicate that the positioning of the β5-β6 loop is necessary for carbapenem hydrolysis by OXA-48. A major difference between the OXA-48 and OXA-163 complexes with carbapenems is that the 214-RIEP-217 deletion in OXA-163 creates a large opening in the active site that is absent in the OXA-48/carbapenem structures. We propose that the larger active site results in less constraint on the conformation of the 6α-hydroxyethyl group in the acyl-enzyme. The acyl-enzyme intermediate assumes multiple conformations, most of which are incompatible with rapid deacylation. Consistent with this hypothesis, molecular dynamics simulations indicate that the most stable complex is formed between OXA-48 and imipenem, which correlates with the OXA-48 hydrolysis of imipenem being the fastest observed. Furthermore, the OXA-163 complexes with imipenem and meropenem are the least stable and show significant conformational fluctuations, which correlates with the slow hydrolysis of these substrates.

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(1)172 of	(10)5 that	(19)3 step	(28)2 increased
(2)40 and	(11)5 the	(20)2 (ESR),	(29)2 it
(3)32 was	(12)4 (HR),	(21)2 (RMR)	(30)2 lactate,
(4)31 null	(13)4 among	(22)2 after	(31)2 or
(5)24 in	(14)4 discrimination	(23)2 at	(32)2 respiratory
(6)8 variability	(15)4 is	(24)2 attributable	(33)2 to
(7)6 constants	(16)4 were	(25)2 between	(34)2 top
(8)6 for	(17)3 enzyme	(26)2 constant	(35)2 which
(9)5 (HR)	(18)3 on	(27)2 equations

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--- WordNet output for rate --- =>価格を評定する, 割合, 率, 歩合, 料金, 値段, 相場, 速度, 度合, 人を〜を思う, みなす, 価値がある, 人を〜とみなす, 科金, 評価する Overview of noun rate The noun rate has 4 senses (first 3 from tagged texts) 1. (68) rate -- (a magnitude or frequency relative to a time unit; "they traveled at a rate of 55 miles per hour"; "the rate of change was faster than expected") 2. (39) rate, charge per unit -- (amount of a charge or payment relative to some basis; "a 10-minute phone call at that rate would cost $5") 3. (1) pace, rate -- (the relative speed of progress or change; "he lived at a fast pace"; "he works at a great rate"; "the pace of events accelerated") 4. rate -- (a quantity or amount or measure considered as a proportion of another quantity or amount or measure; "the literacy rate"; "the retention rate"; "the dropout rate") Overview of verb rate The verb rate has 3 senses (first 3 from tagged texts) 1. (9) rate, rank, range, order, grade, place -- (assign a rank or rating to; "how would you rank these students?"; "The restaurant is rated highly in the food guide") 2. (2) rate -- (be worthy of or have a certain rating; "This bond rates highly") 3. (1) rate, value -- (estimate the value of; "How would you rate his chances to become President?"; "Gold was rated highly among the Romans") --- WordNet end ---