Structural Evidence of Substrate Specificity in Mammalian Peroxidases: Structure of the Thiocyanate Complex with Lactoperoxidase and Its Interactions at 2.4 A Resolution

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2009 Apr 3

PMID 19339248

Citations 17

Authors

Ishfaq Ahmed Sheikh

Amit Kumar Singh

Nagendra Singh

Mau Sinha

S Baskar Singh

Asha Bhushan

Punit Kaur

Alagiri Srinivasan

Sujata Sharma

Tej P Singh

Affiliations

Soon will be listed here.

Abstract

The crystal structure of the complex of lactoperoxidase (LPO) with its physiological substrate thiocyanate (SCN(-)) has been determined at 2.4A resolution. It revealed that the SCN(-) ion is bound to LPO in the distal heme cavity. The observed orientation of the SCN(-) ion shows that the sulfur atom is closer to the heme iron than the nitrogen atom. The nitrogen atom of SCN(-) forms a hydrogen bond with a water (Wat) molecule at position 6'. This water molecule is stabilized by two hydrogen bonds with Gln(423) N(epsilon2) and Phe(422) oxygen. In contrast, the placement of the SCN(-) ion in the structure of myeloperoxidase (MPO) occurs with an opposite orientation, in which the nitrogen atom is closer to the heme iron than the sulfur atom. The site corresponding to the positions of Gln(423), Phe(422) oxygen, and Wat(6)' in LPO is occupied primarily by the side chain of Phe(407) in MPO due to an entirely different conformation of the loop corresponding to the segment Arg(418)-Phe(431) of LPO. This arrangement in MPO does not favor a similar orientation of the SCN(-) ion. The orientation of the catalytic product OSCN(-) as reported in the structure of LPO.OSCN(-) is similar to the orientation of SCN(-) in the structure of LPO.SCN(-). Similarly, in the structure of LPO.SCN(-).CN(-), in which CN(-) binds at Wat(1), the position and orientation of the SCN(-) ion are also identical to that observed in the structure of LPO.SCN.

Citing Articles

Biochemical and Structural Characterisation of a Bacterial Lactoperoxidase.

Pecanac O, Martin C, Savino S, Rozeboom H, Fraaije M, Loncar N Chembiochem. 2024; 26(2):e202400713.

PMID: 39570012 PMC: 11776367. DOI: 10.1002/cbic.202400713.

Reverse Ordered Sequential Mechanism for Lactoperoxidase with Inhibition by Hydrogen Peroxide.

Cupp-Sutton K, Ashby M Antioxidants (Basel). 2021; 10(11).

PMID: 34829517 PMC: 8614691. DOI: 10.3390/antiox10111646.

Structural evidence of the oxidation of iodide ion into hyper-reactive hypoiodite ion by mammalian heme lactoperoxidase.

Singh P, Ahmad N, Yamini S, Singh R, Singh A, Sharma P Protein Sci. 2021; 31(2):384-395.

PMID: 34761444 PMC: 8819834. DOI: 10.1002/pro.4230.

Structure of Yak Lactoperoxidase at 1.55 Å Resolution.

Viswanathan V, Rani C, Ahmad N, Singh P, Sharma P, Kaur P Protein J. 2021; 40(1):8-18.

PMID: 33389415 DOI: 10.1007/s10930-020-09957-2.

Design, Synthesis, Molecular Modeling, and Biological Evaluation of Novel Thiouracil Derivatives as Potential Antithyroid Agents.

Awad S, Zohny Y, Ali S, Mahgoub S, Said A Molecules. 2018; 23(11).

PMID: 30413058 PMC: 6278332. DOI: 10.3390/molecules23112913.

References

Singh A, Singh N, Sharma S, Shin K, Takase M, Kaur P . Inhibition of lactoperoxidase by its own catalytic product: crystal structure of the hypothiocyanate-inhibited bovine lactoperoxidase at 2.3-A resolution. Biophys J. 2009; 96(2):646-54. PMC: 2716474. DOI: 10.1016/j.bpj.2008.09.019. View

Ciaccio C, de Sanctis G, Marini S, Sinibaldi F, Santucci R, Arcovito A . Proton linkage for CO binding and redox properties of bovine lactoperoxidase. Biophys J. 2003; 86(1 Pt 1):448-54. PMC: 1303810. DOI: 10.1016/S0006-3495(04)74121-1. View

Furtmuller P, Jantschko W, Zederbauer M, Jakopitsch C, Arnhold J, Obinger C . Kinetics of interconversion of redox intermediates of lactoperoxidase, eosinophil peroxidase and myeloperoxidase. Jpn J Infect Dis. 2004; 57(5):S30-1. View

NICHOL A, Angel L, Moon T, Clezy P . Lactoperoxidase haem, an iron-porphyrin thiol. Biochem J. 1987; 247(1):147-50. PMC: 1148381. DOI: 10.1042/bj2470147. View

Geissler P, Dellago C, Chandler D, Hutter J, Parrinello M . Autoionization in liquid water. Science. 2001; 291(5511):2121-4. DOI: 10.1126/science.1056991. View

Jones T, Zou J, Cowan S, Kjeldgaard M . Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr A. 1991; 47 ( Pt 2):110-9. DOI: 10.1107/s0108767390010224. View

ORAM J, Reiter B . The inhibition of streptococci by lactoperoxidase, thiocyanate and hydrogen peroxide. The oxidation of thiocyanate and the nature of the inhibitory compound. Biochem J. 1966; 100(2):382-8. PMC: 1265146. DOI: 10.1042/bj1000382. View

Fiedler T, Davey C, Fenna R . X-ray crystal structure and characterization of halide-binding sites of human myeloperoxidase at 1.8 A resolution. J Biol Chem. 2000; 275(16):11964-71. DOI: 10.1074/jbc.275.16.11964. View

Fenna R, Zeng J, Davey C . Structure of the green heme in myeloperoxidase. Arch Biochem Biophys. 1995; 316(1):653-6. DOI: 10.1006/abbi.1995.1086. View

10.

Mohammed O, Pines D, Dreyer J, Pines E, Nibbering E . Sequential proton transfer through water bridges in acid-base reactions. Science. 2005; 310(5745):83-6. DOI: 10.1126/science.1117756. View

11.

Crull G, Goff H . NMR relaxation studies of the interaction of thiocyanate with lactoperoxidase. J Inorg Biochem. 1993; 50(3):181-92. DOI: 10.1016/0162-0134(93)80024-4. View

12.

Goldstein F . The colorimetric determination of thiocyanate in whole blood. J Biol Chem. 1950; 187(2):523-7. View

13.

Hoogendoorn H, Piessens J, Scholtes W, Stoddard L . Hypothiocyanite ion; the inhibitor formed by the system lactoperoxidase-thiocyanate-hydrogen peroxide. I. Identification of the inhibiting compound. Caries Res. 1977; 11(2):77-84. DOI: 10.1159/000260252. View

14.

Fiedler T, Fenna R . Human myeloperoxidase: structure of a cyanide complex and its interaction with bromide and thiocyanate substrates at 1.9 A resolution. Biochemistry. 2001; 40(46):13990-7. DOI: 10.1021/bi0111808. View

15.

Shindler J, Bardsley W . Steady-state kinetics of lactoperoxidase with ABTS as chromogen. Biochem Biophys Res Commun. 1975; 67(4):1307-12. DOI: 10.1016/0006-291x(75)90169-2. View

16.

McCoy A, Grosse-Kunstleve R, Storoni L, Read R . Likelihood-enhanced fast translation functions. Acta Crystallogr D Biol Crystallogr. 2005; 61(Pt 4):458-64. DOI: 10.1107/S0907444905001617. View

17.

DePillis G, Ozaki S, Kuo J, Maltby D, Ortiz de Montellano P . Autocatalytic processing of heme by lactoperoxidase produces the native protein-bound prosthetic group. J Biol Chem. 1997; 272(14):8857-60. DOI: 10.1074/jbc.272.14.8857. View

18.

Mowat C, Rothery E, Miles C, McIver L, Doherty M, Drewette K . Octaheme tetrathionate reductase is a respiratory enzyme with novel heme ligation. Nat Struct Mol Biol. 2004; 11(10):1023-4. DOI: 10.1038/nsmb827. View

19.

Tahboub Y, Galijasevic S, Diamond M, Abu-Soud H . Thiocyanate modulates the catalytic activity of mammalian peroxidases. J Biol Chem. 2005; 280(28):26129-36. DOI: 10.1074/jbc.M503027200. View

20.

Wolfson L, Sumner S . Antibacterial Activity of the Lactoperoxidase System: A Review. J Food Prot. 2019; 56(10):887-892. DOI: 10.4315/0362-028X-56.10.887. View