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- W3136115992 abstract "Abstract TEM-1 β-lactamase degrades β-lactam antibiotics with a strong preference for penicillins. Sequence reconstruction studies indicate that it evolved from ancestral enzymes that degraded a variety of β-lactam antibiotics with moderate efficiency. This generalist to specialist conversion involved more than 100 mutational changes, but conserved fold and catalytic residues, suggesting a role for dynamics in enzyme evolution. Here, we develop a conformational dynamics computational approach to rationally mold a protein flexibility profile on the basis of a hinge-shift mechanism. By deliberately weighting and altering the conformational dynamics of a putative Precambrian β-lactamase, we engineer enzyme specificity that mimics the modern TEM-1 β-lactamase with only 21 amino acid replacements. Our conformational dynamics design thus re-enacts the evolutionary process and provides a rational allosteric approach for manipulating function while conserving the enzyme active site." @default.
- W3136115992 created "2021-03-29" @default.
- W3136115992 creator A5006882336 @default.
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- W3136115992 creator A5085151546 @default.
- W3136115992 date "2021-03-25" @default.
- W3136115992 modified "2023-10-18" @default.
- W3136115992 title "Hinge-shift mechanism as a protein design principle for the evolution of β-lactamases from substrate promiscuity to specificity" @default.
- W3136115992 cites W1587767001 @default.
- W3136115992 cites W1861406683 @default.
- W3136115992 cites W1968702502 @default.
- W3136115992 cites W1976499671 @default.
- W3136115992 cites W1980504350 @default.
- W3136115992 cites W1983186463 @default.
- W3136115992 cites W1986743126 @default.
- W3136115992 cites W1987635163 @default.
- W3136115992 cites W1993400812 @default.
- W3136115992 cites W1993646374 @default.
- W3136115992 cites W1997078773 @default.
- W3136115992 cites W2001641653 @default.
- W3136115992 cites W2013253738 @default.
- W3136115992 cites W2016466447 @default.
- W3136115992 cites W2016666153 @default.
- W3136115992 cites W2026387425 @default.
- W3136115992 cites W2028702957 @default.
- W3136115992 cites W2031117172 @default.
- W3136115992 cites W2031239680 @default.
- W3136115992 cites W2046200242 @default.
- W3136115992 cites W2049251120 @default.
- W3136115992 cites W2069777230 @default.
- W3136115992 cites W2070268621 @default.
- W3136115992 cites W2083120667 @default.
- W3136115992 cites W2085277871 @default.
- W3136115992 cites W2085347260 @default.
- W3136115992 cites W2093381148 @default.
- W3136115992 cites W2097029677 @default.
- W3136115992 cites W2108267147 @default.
- W3136115992 cites W2109441358 @default.
- W3136115992 cites W2110847661 @default.
- W3136115992 cites W2118265845 @default.
- W3136115992 cites W2120513776 @default.
- W3136115992 cites W2121867408 @default.
- W3136115992 cites W2124019798 @default.
- W3136115992 cites W2124026197 @default.
- W3136115992 cites W2128312954 @default.
- W3136115992 cites W2134286200 @default.
- W3136115992 cites W2135900956 @default.
- W3136115992 cites W2142595184 @default.
- W3136115992 cites W2145317354 @default.
- W3136115992 cites W2147872249 @default.
- W3136115992 cites W2150842398 @default.
- W3136115992 cites W2151496242 @default.
- W3136115992 cites W2151693813 @default.
- W3136115992 cites W2154714625 @default.
- W3136115992 cites W2159802673 @default.
- W3136115992 cites W2161311439 @default.
- W3136115992 cites W2163341755 @default.
- W3136115992 cites W2168142063 @default.
- W3136115992 cites W2168798454 @default.
- W3136115992 cites W2169707043 @default.
- W3136115992 cites W2169821755 @default.
- W3136115992 cites W2180229411 @default.
- W3136115992 cites W2234497665 @default.
- W3136115992 cites W2265800909 @default.
- W3136115992 cites W2313116527 @default.
- W3136115992 cites W2404280981 @default.
- W3136115992 cites W2438101437 @default.
- W3136115992 cites W2480986332 @default.
- W3136115992 cites W2561072227 @default.
- W3136115992 cites W2739236546 @default.
- W3136115992 cites W2751446368 @default.
- W3136115992 cites W2752784998 @default.
- W3136115992 cites W2766508684 @default.
- W3136115992 cites W2768035568 @default.
- W3136115992 cites W2777639606 @default.
- W3136115992 cites W2786871622 @default.
- W3136115992 cites W2791743062 @default.
- W3136115992 cites W2796690990 @default.
- W3136115992 cites W2805565876 @default.
- W3136115992 cites W2883581091 @default.
- W3136115992 cites W2902285630 @default.
- W3136115992 cites W2903084665 @default.
- W3136115992 cites W2911398658 @default.
- W3136115992 cites W2917580301 @default.
- W3136115992 cites W2936990387 @default.
- W3136115992 cites W2950308590 @default.
- W3136115992 cites W2990692327 @default.
- W3136115992 cites W3007100485 @default.
- W3136115992 cites W3007324177 @default.
- W3136115992 cites W4210675630 @default.
- W3136115992 cites W4243995664 @default.
- W3136115992 cites W4247080900 @default.
- W3136115992 cites W4248872320 @default.
- W3136115992 doi "https://doi.org/10.1038/s41467-021-22089-0" @default.
- W3136115992 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7994827" @default.