Isomerases catalyze bond rearrangement within a molecule.

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• Isomerases catalyze bond rearrangement within a
  molecule.
• Subclasses Which type of isomerization?

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Essential groups amino acid side chains,
non-covalent intermediates Glu, His, Lys as
acids and bases Arg, Mg2 Aminoacyl-tRNA
synthetases
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Glu, His triose phosphate isomerase
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Glu, His triose phosphate isomerase
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Glu, His triose phosphate isomerase
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Glu, His triose phosphate isomerase Glu is the
essential base and needs to be deprotonated, pH gt
pKa (6.5). His is an essential hydrogen bonding
partner, very short (O-O 2.4-2.5 A), strong
(50-100 kJ/mol) H-bonds are formed LBHB
(low-barrier hydrogen bond).
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His, Lys mandelate racemase
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His, Lys mandelate racemase Partial turnover in
D2O After turnover of 5.6 (R)-mandelate only
0.2 of the remaining substrate has exchanged H
to D (4). After turnover of 6.1 (S)-mandelate
3.5 of the remaining substrate has exchanged H
to D (57). D is incorporated at more than 97
into the products. Two bases of different types
are involved.
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His, Lys mandelate racemase
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His, Lys mandelate racemase
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His, Lys mandelate racemase A pKa of 6 was
observed for Lys166. The reason for this
unusually low pKa could be the nearby positively
charged Lys164.
Atrolactate H gt Me exchange compared to mandelate
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Essential groups amino acid side chains,
covalent intermediates Tyr Topoisomerase
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Tyr Topoisomerase IATP-independent breakage of
single-stranded DNA, followed by passage and
rejoining IIATP-dependent breakage, passage and
rejoining of double-stranded DNA. Can introduce
negative superhelical turns into double-stranded
circular DNA.
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Tyr Topoisomerase Two DNA double helices are
nicked, one strand of each exchanged, and
religated.
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Tyr Topoisomerase The nucleophile Tyr723 is
assisted by a water and Arg590 (positive charges
in the vicinity lower the pKa of Tyr).
Lys532 and Arg488 polarize the phosphate.
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Essential groups cofactors Coenzyme B12
Rearrangement of C-C bonds via radicals.
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Coenzyme B12 Methylmalonyl CoA mutase
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Coenzyme B12 Methylmalonyl CoA mutase
Hydrolysis of 2-67 in water can produce succinic
acid, but only 4. The highly reactive
intermediates, radical, anionic, or cationic,
prevent higher specificity. The enzyme directs
the reaction by preventing wrong products.