Effect of covalent links on the structure, spectra, and redox properties of myeloperoxidase - A density functional study

被引:6
作者
Devarajan, Ajitha [1 ,2 ]
Gaenko, Alexander V. [1 ,3 ]
Ryde, Ulf [1 ]
机构
[1] Lund Univ, Dept Theoret Chem, Ctr Chem, SE-22100 Lund, Sweden
[2] Univ N Dakota, Dept Chem, Grand Forks, ND 58201 USA
[3] Tech Univ, St Petersburg State Inst Technol, St Petersburg 190013, Russia
关键词
mammalian peroxidases; electronic spectra; reduction potentials; compound II; time-dependent density functional theory;
D O I
10.1016/j.jinorgbio.2008.01.031
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The enzyme myeloperoxidase shows several unusual properties compared to other peroxidases, e.g. a red-shifted absorption spectrum and a peroxidase activity towards chloride. It has been suggested that this is caused by the unusual covalent links between the heme group and the surrounding protein, but whether it is caused by the two ester links to Glu-242 and Asp-94 or the sulfonium ion linkage to Met-243 is unclear. To investigate these suggestions, we have used density functional theory to study the structure, spectra, and reduction potential of 25 models of myeloperoxidase in the reduced (Fe-II) and oxidized (Fe-III) states, as well as in the compound I (formally (FeO)-O-V) and II ((FeO)-O-IV or (FeOH)-O-IV) states, using appropriate models of the linkages to the Asp, Glu, and Met residues (including the backbone connection between Glu-242 and Met-243) in varying combinations. The calculated spectral shifts indicate that both the ester and sulfonium linkages play a role in the spectral shift. On the other hand, the sulfonium linkage seems to be mainly responsible for the high positive reduction potential for the both ferric/ferrous and compound I/II couples of myeloperoxidase. (c) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:1549 / 1557
页数:9
相关论文
共 49 条
[1]   A COMPARISON OF THE ACCURACY OF DIFFERENT FUNCTIONALS [J].
BAUSCHLICHER, CW .
CHEMICAL PHYSICS LETTERS, 1995, 246 (1-2) :40-44
[2]   DENSITY-FUNCTIONAL THERMOCHEMISTRY .3. THE ROLE OF EXACT EXCHANGE [J].
BECKE, AD .
JOURNAL OF CHEMICAL PHYSICS, 1993, 98 (07) :5648-5652
[3]   DENSITY-FUNCTIONAL EXCHANGE-ENERGY APPROXIMATION WITH CORRECT ASYMPTOTIC-BEHAVIOR [J].
BECKE, AD .
PHYSICAL REVIEW A, 1988, 38 (06) :3098-3100
[4]   On the status of ferryl protonation [J].
Behan, Rachel K. ;
Green, Michael T. .
JOURNAL OF INORGANIC BIOCHEMISTRY, 2006, 100 (04) :448-459
[5]   Remarks about protein structure precision [J].
Cruickshank, DWJ .
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 1999, 55 :583-601
[7]   Auxiliary basis sets for main row atoms and transition metals and their use to approximate Coulomb potentials [J].
Eichkorn, K ;
Weigend, F ;
Treutler, O ;
Ahlrichs, R .
THEORETICAL CHEMISTRY ACCOUNTS, 1997, 97 (1-4) :119-124
[8]   AUXILIARY BASIS-SETS TO APPROXIMATE COULOMB POTENTIALS [J].
EICHKORN, K ;
TREUTLER, O ;
OHM, H ;
HASER, M ;
AHLRICHS, R .
CHEMICAL PHYSICS LETTERS, 1995, 240 (04) :283-289
[9]  
Fenna R.E., 2001, HDB METALLOPROTEINS, V1, P211
[10]  
FIELDER TJ, 2000, J BIOL CHEM, V275, P11964