Abstract
Carbonic anhydrase binds a zinc ion in a hydrophobic active site using the imidazole groups of three histidine residues. The natural role of carbonic anhydrase is to catalyze the reversible hydration of carbon dioxide to bicarbonate, but it also catalyzes hydrolysis of esters with moderate enantioselectivity. Replacing the active-site zinc with manganese yielded manganese-substituted carbonic anhydrase (CA[Mn]), which shows peroxidase activity with a bicarbonate-dependent mechanism. In the presence of bicarbonate and hydrogen peroxide, CA[Mn] catalyzed the efficient oxidation of o-dianisidine with k cat /K M = 1.4 × 106 M−1s−1, which is comparable to that for horseradish peroxidase, k cat /K M = 57 × 106 M−1s−1. CA[Mn] also catalyzed the moderately enantioselective epoxidation of olefins to epoxides (E = 5 for p-chlorostyrene). This enantioselectivity is similar to that for natural heme-based peroxidases, but has the advantage that CA[Mn] avoids formation of aldehyde side products. CA[Mn] degrades during the epoxidation, limiting the yield of the epoxidations to <12%. Replacement of active-site residues Asn62, His64, Asn67, Gln92, or Thr200 with alanine by site-directed mutagenesis decreased the enantioselectivity showing that the active site controls enantioselectivity of the epoxidation.
Abbreviations
- Ala:
-
Alanine
- Asn:
-
Asparagine
- Asp:
-
Aspartic acid
- BES:
-
N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid
- CA:
-
Carbonic anhydrase
- CA[Mn]:
-
Manganese-substituted bovine carbonic anhydrase mixture of isozymes
- CAII[Mn]:
-
Manganese-substituted bovine carbonic anhydrase isoenzyme II
- CiP:
-
Peroxidase from Coprinus cinereus
- CPO:
-
Chloroperoxidase from Caldariomyces fumago
- Mn:
-
Manganese
- E :
-
Enantioselectivity
- ee:
-
Enantiomeric excess
- ESI-MS:
-
Electrospray ionization mass spectrometry
- Gln:
-
Glutamine
- Glu:
-
Glutamic acid
- hCAII:
-
Human carbonic anhydrase isozyme II
- His:
-
Histidine
- HRP:
-
Horseradish peroxidase
- ICP-AES:
-
Inductively coupled plasma atomic emission spectrometry
- k cat :
-
Catalytic constant
- K M :
-
Michaelis constant
- Leu:
-
Leucine
- PNPA:
-
4-Nitrophenyl acetate
- Ser:
-
Serine
- Trp:
-
Tryptophan
- Thr:
-
Threonine
- TOF:
-
Turnover frequency
- TTN:
-
Total turnover number
- Val:
-
Valine
- VClPO:
-
Vanadium chloroperoxidase
References
Bäckvall J-E (ed) (2004) Modern oxidation methods. Wiley-VCH, New York, p 295
Strukul G (ed) (1992) Catalytic oxidation with hydrogen peroxide as oxidant. Springer, Boston
Lu Y (2005) Curr Opin Chem Biol 9:118
Letondor C, Ward TR (2006) ChemBioChem 7:1845
Thomas CM, Ward TR (2005) Chem Soc Rev 34:337
Wilson ME, Whitesides GM (1978) J Am Chem Soc 100:306
Lin CC, Lin CW, Chan ASC (1999) Tetrahedron: Asymmetry 10:1887
Collot J, Gradinaru J, Humbert N, Skander M, Zocchi A, Ward TR (2003) J Am Chem Soc 125:9030
Skander M, Humbert N, Collot J, Gradinaru J, Klein G, Loosli A, Sauser J, Zocchi A, Gilardoni F, Ward TR (2004) J Am Chem Soc 126:1441
Skander M, Malan C, Ivanova A, Ward TR (2005) Chem Commun 2005:4815
Ward TR (2005) Chem Eur J11:3798
Letondor C, Humbert N, Ward TR (2005) Proc Natl Acad Sci USA 102:4683
Letondor C, Pordea A, Humbert N, Ivanova A, Mazurek S, Novic M, Ward TR (2006) J Am Chem Soc 128:8320
Klein G, Humbert N, Gradinaru J, Ivanova A, Gilardoni F, Rusbandi UE, Ward TR (2005) Angew Chem Int Ed 44:7764
Roelfes G, Feringa BL (2005) Angew Chem Int Ed 44:3230
Roelfes G, Boersma AJ, Feringa BL (2006) Chem Commun 2006:635
Reetz MT, Jiao N (2006) Angew Chem Int Ed 45:2416
Carey JR, Ma SK, Pfister TD, Garner DK, Kim HK, Abramite JA, Whang Z, Guo Z, Lu Y (2004) J Am Chem Soc 126:10812
Ohashi M, Koshiyama T, Ueno T, Yanase M, Fujii H, Watanabe Y (2003) Angew Chem Int Ed 42:1005
Ory JJ, Mazhary A, Kuang H, Davies RR, Distefano MD, Banaszak LJ (1998) Prot Eng 11:253
Bertucci C, Botteghi C, Giunta D, Marchetti M, Paganelli S (2002) Adv Synth Catal 344:556
Ueno T, Suzuki M, Goto T, Matsumoto T, Nagayama K, Watanabe Y (2004) Angew Chem Int Ed 4:2527
Yamamura K, Kaiser ET (1976) J Chem Soc Chem Commun 1976:830
da Silva GFZ, Ming L-J (2005) J Am Chem Soc 127:16380
Bakker M, van Rantwijk F, Sheldon RA (2002) Can J Chem 80:622
van de Velde F, Könemann L, van Rantwijk F, Sheldon RA (1998) Chem Commun 1998:1891
Haering D, Schueler E, Adam W, Saha-Moeller CR, Schreier P (1999) J Org Chem 64:832
Gomes CM, Frazão C, Xavier AV, Legall J, Teixeira M (2002) Prot Sci 11:707
Supuran CT (2007) Curr Topics Med Chem 7:825
Eriksson AE, Kylsten PM, Jones TA, Liljas A (1998) Proteins 4:283
Håkansson K, Wehnert A, Liljas A (1994) Acta Crystallogr D Biol Crystallogr 50:93
Jain A, Whitesides GM, Alexander RS, Christianson DW (1994) J Med Chem 37:2100
Chênevert R, Letourneau M (1990) Can J Chem 68:314
Gould SM, Tawfik DS (2005) Biochemistry 44:5444
Kidani Y, Hirose J (1976) J Biochem 79:43
Kidani Y, Hirose J (1977) J Biochem 81:1383
Wilkins RG, Williams KR (1974) J Am Chem Soc 96:2241
Okrasa K, Kazlauskas RJ (2006) Chem Eur J 12:1587
McCall KA, Fierke CA (2004) Biochemistry 43:3979
Lanir A, Gradstajn S, Navon G (1975) Biochemistry 14:242
Lane BS, Burgess K (2001) J Am Chem Soc 123:2933
Lane BS, Burgess K (2003) Chem Rev 103:2457
Lane BS, Vogt M, DeRose VJ, Burgess K (2002) J Am Chem Soc 124:11946
Tong K-H, Wong K-Y, Chan TH (2003) Org Lett 5:3423
Yim MB, Berlett BS, Chock PB, Stadtman ER (1990) Proc Natl Acad Sci USA 87:394
Fernández-Gacio A, Codina A, Fastrez J, Riant O, Soumillion P (2006) ChemBioChem 7:1013
Claiborne A, Fridovich I (1979) Biochemistry 18:2324
Keyhani J, Keyhani E, Zarchipour S, Tayefi-Nasrabadi H, Einollahi N (2005) Biochim Biophys Acta 1722:312
Ugarova NN, Lebedeva OV, Berezin V (1981) J Mol Catal 13:215
Zou P, Schrempf H (2000) Eur J Biochem 267:2840
Gabler M, Hensel M, Fisher L (2000) Enzym Microb Technol 27:605
Kernohan JC (1965) Biochim Biophys Acta 96:304
ten Brink HB, Dekker HL, Schoemaker HE, Wever R (2000) J Inorg Biochem 80:91
Sossong TM, Khangulov SV, Cavalli RC, Soprano DR, Dismukes GC, Ash DE (1997) J Biol Inorg Chem 2:433
Tuynman A, Spelberg JL, Kooter IM, Schoemaker HE, Wever R (2000) J Biol Chem 275:3025
Patel (ed) R (2000) Stereoselective biocatalysis. Marcel Dekker, New York
Zaks A, Dodds DR (1995) J Am Chem Soc 117:10419
Green MK, Vestling MM, Johnston MV, Larsen BS (1998) Anal Biochem 260:204
Kureshy RI, Khan NH, Abdi SHR, Singh S, Ahmed I, Shukla RS, Jasra RV (2003) J Catal 219:1
Led JJ, Neesgaard E, Johansen J (1982) FEBS Lett 147:74
Hage R, Iburg JE, Kerschner J, Koek JH, Lempers ELM, Martens RJ, Racherla US, Russell SW, Swarthoff T (1994) Nature 369:637
Kuhne L, Odermatt J, Wachter T (2000) Holzforschung 54:407
Cherry JR, Lamsa MH, Schneider P, Vind J, Svendsen A, Jones A, Pedersen AH (1999) Nature Biotechnol 17:379
Abel EW, Stone FGA, Wilkinson G (ed) (1995) Comprehensive organometallic chemistry II, Pergamon, New York, p 1097vol 12.
Ojima I (ed) (2000) Catalytic asymmetric synthesis, 2nd edn, Wiley-VCH, New York, p 231vol 6A.
Carrea G, Colonna S, Kelly DR, Lazcano A, Ottolina G, Roberts SM (2005) Trends Biotechnol 23:507
Jing Q, Okrasa K, Kazlauskas RJ (2008) Chem Eur J, accepted.
Author information
Authors and Affiliations
Rights and permissions
Copyright information
© 2008 Springer-Verlag London
About this chapter
Cite this chapter
Jing, Q., Okrasa, K., Kazlauskas, R.J. (2008). Manganese-Substituted α-Carbonic Anhydrase as an Enantioselective Peroxidase. In: Topics in Organometallic Chemistry. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3418_2008_1
Download citation
DOI: https://doi.org/10.1007/3418_2008_1
Published:
Publisher Name: Springer, Berlin, Heidelberg