Lyases make or break bonds without redox or hydrolytic steps'

1

• Lyases make or break bonds without redox or
  hydrolytic steps.
• Subclasses Which type of bond is broken?

2

• Essential groups amino acid side chains,
  covalent intermediates
• Cys Cyanide hydratase (nucleophilic attack,
  comparable to cysteine proteases)
• Lys Aldolase

3

• Lys Aldolase
• Reverse reaction Glyceral-3-phosphate can add to
  the enamine tautomer of the imine formed by
  lysine and glyceron-3-phosphate
• older names glycerolaldehyde-3-phosphate and
  dihydroxyacetone phosphate

The nucleophilic attack is enabled by the enamine
form of the glycerone ketimine.
4

• Essential groups metal ions
• Fe-S aconitase
• Zn aldolase, carbonate dehydratase (carbonic
  anhydrase)
• Mg Adenylate cyclase

5

• Fe-S aconitase

6

• Fe-S aconitase
• Iron-sulfur cluster in an unusual role iron as
  lewis acid instead of redox partner.

Fe4S4Cys3
Usual Fe4S4Cys4 in redox proteins
7

• Fe-S aconitase

Fe4S4Cys3
8

• Essential groups cofactors
• PLP decarboxylases (amino acids)
• Thiamine decarboxylases
• NAD urocanase
• MIO histidine ammonia-lyase
• Coenzyme B12 glycerol dehydratase

9

• PLP Alliinase (b,g lyase)

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Lachrymatory factor synthase
10

• PLP Alliinase
• b,g-lyase
• Amino group of the educt has to be deprotonated
  for the reaction with PLP.

11

• PLP Alliinase

12

• Thiamine decarboxylases
• Forming the covalent intermediate and cleavage of
  the C-C bond.

13

• Thiamine decarboxylases
• The easy finish release ethanal (EC 4.1.1.1)

14

• Thiamine decarboxylases
• The tricky finish reduce lipoamide and conserve
  energy
• (EC 1.2.4.1).

15

• NAD urocanase (EC 4.2.1.49)
• An unusual use of a redox cofactor.

16

• NAD urocanase
• Pyridine is an electron poor aromat, imidazol an
  electron rich aromat
• Electrophilic attack of NAD on urocanate.

17

• MIO histidine ammonia-lyase

Why not use PLP, the cofactor which usually has
to take care of amino acid metabolism? Problem
Imidazole is an electron rich aromat, proton
abstraction next to it is unfavorable.
18

• MIO histidine ammonia-lyase
• Autocatalytic formation of the protein bound
  cofactor 4-methylidene-imidazole-5-one (MIO).

19

• MIO histidine ammonia-lyase
• Electrophilic attack on the imidazole ring.