The hydrogen chemistry of the FeMo-co active site of nitrogenase

被引:65
作者
Dance, I [1 ]
机构
[1] Univ New S Wales, Sch Chem, Sydney, NSW 2052, Australia
关键词
D O I
10.1021/ja0504946
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The chemical mechanism by which nitrogenase enzymes catalyze the hydrogenation of N-2 (and other multiply bonded substrates) at the (NFe7MoS9)-Fe-c(homocitrate) active site (FeMo-co) is unknown, despite the accumulation of much data on enzyme reactivity and the influences of key amino acids surrounding FeMo-co. The mutual influences of H-2, substrates, and the inhibitor CO on reactivity are key experimental tests for postulated mechanisms. Fundamental to all aspects of mechanism is the accumulation of H atoms (from e(-) + H+) on FeMo-co, and the generation and influences of coordinated H2. Here, I argue that the first introduction of H is via a water chain terminating at water 679 (PDB structure 1M1N, Azotobacter vinelandii) to one of the mu(3)-S atoms (S3B) of FeMo-co. Next, using validated density functional calculations of a full chemical representation of FeMo-co and its connected residues (alpha-275(Cys), alpha-442(His)), I have characterized more than 80 possibilities for the coordination of up to three H atoms, and H-2, and H + H-2, on the S2A, Fe2, S2B, Fe6, S3B domain of FeMo-co, which is favored by recent targeted mutagenesis results. Included are calculated reaction profiles for movements of H atoms (between S and Fe, and between Fe and Fe), for the generation of Fe-H-2, for association and dissociation of Fe-H-2 at various reduction levels, and for H/H-2 exchange. This is new hydrogen chemistry on an unprecedented coordination frame, with some similarities to established hydrogen coordination chemistry, and with unexpected and unprecedented structures such as Fe(S)(3)(H-2)(2)(H) octahedral coordination. General principles for the hydrogen chemistry of FeMo-co include (1) the stereochemical mobility of H bound to mu(3)-S, (2) the differentiated endo- and exo- positions at Fe for coordination of H and/or H-2, and (3) coordinative allosteric influences in which structural and dynamic aspects of coordination at one Fe atom are affected by coordination at another Fe atom, and by H on S atoms. Evidence of end-differentiation in FeMo-co is described, providing a rationale for the occurrence of Mo. The reactivity results are discussed in the context of the Thorneley-Lowe scheme for nitrogenase reactions, and especially the scheme for the HID reaction (2H(+) + 2e(-) + D-2 -> 2HD), using a model containing an H-entry site and at least two coordinative sites on FeMo-co. I propose that S3B is the H-entry site, suggest details for the H+ shuttle to S3B and subsequent movement of H atoms around FeMo-co preparatory to the binding and hydrogenation of N2 and other substrates, and suggest how H could be transferred to an alkyne substrate. I propose that S2B (normally hydrogen bonded to alpha-195(His)) has a modulatory function and is not an H-entry site. Finally, the recent first experimental trapping of a hydrogenated intermediate with EPR and ENDOR characterization is discussed, leading to a consensual model for the intermediate.
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页码:10925 / 10942
页数:18
相关论文
共 102 条
[91]  
2-9
[92]   The nitrogenase catalyzed N2 dependent HD formation:: a model reaction and its significance for the FeMoco function [J].
Sellmann, D ;
Fürsattel, A ;
Sutter, J .
COORDINATION CHEMISTRY REVIEWS, 2000, 200 :545-561
[93]   Binding H2, N2, H-, and BH3 to transition-metal sulfur sites:: Synthesis and properties of [Ru(L)(PR3)(N2Me2S2)] complexes (L = η2-H2, H-, BH3; R = Cy, iPr) [J].
Sellmann, D ;
Hille, A ;
Heinemann, FW ;
Moll, M ;
Reiher, M ;
Hess, BA ;
Bauer, W .
CHEMISTRY-A EUROPEAN JOURNAL, 2004, 10 (17) :4214-4224
[94]  
Sellmann D, 1997, NEW J CHEM, V21, P681
[95]   Nitrogen fixation by nitrogenases: A quantum chemical study [J].
Siegbahn, PEM ;
Westerberg, J ;
Svensson, M ;
Crabtree, RH .
JOURNAL OF PHYSICAL CHEMISTRY B, 1998, 102 (09) :1615-1623
[96]   Structure, function, and biosynthesis of the metallosulfur clusters in nitrogenases [J].
Smith, BE .
ADVANCES IN INORGANIC CHEMISTRY, VOL 47: IRON-SULFUR PROTEINS, 1999, 47 :159-218
[97]  
Stavrev KK, 1998, INT J QUANTUM CHEM, V70, P1159
[98]   Theoretical studies of biological nitrogen fixation. I. Density functional modeling of the Mo-site of the FeMo-cofactor [J].
Szilagyi, RK ;
Musaev, DG ;
Morokuma, K .
INORGANIC CHEMISTRY, 2001, 40 (04) :766-775
[99]   Theoretical studies of biological nitrogen fixation. Part II. Hydrogen bonded networks as possible reactant and product channels [J].
Szilagyi, RK ;
Musaev, DG ;
Morokuma, K .
JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM, 2000, 506 :131-146
[100]  
Thorneley RNF., 1985, Metal Ions Biol, P221