Metalloenzymes and Electrophilic Catalysis


Enzymes perform a number of remarkable synthetic transformations at neutral pH and ambient temperatures. Many enzymes employ metal ions to aid in electrophilic catalysis. Zinc, the commonest Lewis acid in biochemistry, is an essential cofactor in over 300 enzymes.

Keywords: general acid catalysis; specific acid catalysis; lewis acid catalysis; non‐redox metalloenzymes

Figure 1.

Schematic energy profile diagrams representing the addition of nucleophile to ethylene oxide [I] under (a) specific base catalysis and (b) specific acid catalysis.

Figure 2.

Schematic representation of the ring opening of ethylene oxide [I] facilitated by simultaneous general acid and base catalysis.

Figure 3.

Schematic representation of a simplified mechanism of carbonic anhydrase. Hydrogen‐bonding interactions are indicated with dotted lines, while for clarity only one of the bridging water molecules between the metal centre and His64 is shown.

Figure 4.

Schematic representation of the mechanism of action of carboxypeptidase A.

Figure 5.

The proposed mechanism of action of aconitase.

Figure 6.

Proposed mechanism of action of kidney bean purple acid phosphatase, with hydrogen bonds indicated by dotted lines (M=Fe(ii) or Zn(ii)).

Figure 7.

Schematic representation of the most recently proposed mechanism for the mechanism of action of urease. Hydrogen‐bonding interactions are indicated by dotted lines.



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Bertini I, Gray HB, Lippard SJ and Valentine JS (1994) Bioinorganic Chemistry. Sausalito, CA: University Science Books.

Ciurli S, Benini S, Rypniewski WR et al. (1999) Structural properties of the nickel ions in urease: novel insights into the catalytic and inhibition mechanisms. Coordination Chemistry Reviews 190–192: 331–355.

Cronin L, Foxon SP, Lusby PJ and Walton PH (2001) Synthesis and structures of M(L)(X)BPh4 complexes {M=Co(II), Zn(II); L=cis‐1,3,5‐tris[3‐(2‐furyl)prop‐2‐enylideneamino]cyclohexane, X=OAc, NO3}; structural models of the active site of carbonic anhydrase. Journal of Biological Inorganic Chemistry 6: 367–377.

Fersht A (1999) Structure and Mechanism in Protein Science. New York: WH Freeman.

Jabri E, Carr MB, Hausinger RP and Karplus PA (1995) The crystal structure of urease from Klebsiella aerogenes. Science 268: 998–1004.

Jedrzejas MJ and Setlow P (2001) Comparison of the binuclear metalloenzymes diphosphoglycerate‐independent phosphoglycerate mutase and alkaline phosphatase: their mechanism of catalysis via a phosphoserine intermediate. Chemical Reviews 101: 607–618.

Kühnel K and Luisi BF (2001) Crystal structure of the Escherichia coli RNA degradosome component enolase. Journal of Molecular Biology 313: 583–592.

Lindskog S (1997) Structure and mechanism of carbonic anhydrase. Pharmacology and Therapeutics 74: 1–20.

Lloyd SJ, Lauble H, Prasad GS and Stout CD (1999) The mechanism of aconitase: 1.8 Å resolution crystal structure of the S642A complex. Protein Science 8: 2655–2662.

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Further Reading

Bertini I, Gray HB, Lippard SJ and Valentine JS (1994) Bioinorganic Chemistry. Sausalito, CA: University Science Books.

Fersht A (1999) Structure and Mechanism in Protein Science. New York: WH Freeman.

Fraústo da Silva JJR and Williams RJP (1991) The Biological Chemistry of the Elements. Oxford: Clarendon Press.

Isaacs N (1995) Physical Organic Chemistry. Singapore: Longman.

Page M and Williams A (1997) Organic and Bio‐organic Mechanism. Singapore: Longman.

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How to Cite close
Eames, Jason, and Watkinson, Michael(May 2005) Metalloenzymes and Electrophilic Catalysis. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0000724]