Active site electronic structure contributions

These enzymes continue to be the subject of intense research efforts, and this is a direct result of their unusual geometric and electronic structures, their key roles in the global C, N and S cycles, their pharmacological importance, and their importance in human health. This volume will detail how spectroscopy, structure, electrochemistry and theory have been used to develop a comprehensive description of the active site electronic structure contributions to reactivity in pyranopterin Mo enzymes and the Mo-dependent nitrogenase. A particular emphasis is placed on how these important studies have been used to reveal critical components of enzyme mechanisms. 

Active Site Electronic Structure Contributions to Reactivity... 

Lowery MD, Guckert JA, Gebhard MS, Solomon El. Active-site electronic structure contributions to electron-transfer pathways in rubredoxin and plastocyanin direct versus superexchange. J Am Chem Soc 2002 115 3012-3013. 

The initial contribution to this volume provides a detailed overview of how spectroscopy and computations have been used in concert to probe the canonical members of each pyranopterin Mo enzyme family, as well as the pyranopterin dithiolene ligand itself. The discussion focuses on how a combination of enzyme geometric structure, spectroscopy and biochemical data have been used to arrive at an understanding of electronic structure contributions to reactivity in all of the major pyranopterin Mo enzyme families. A unique aspect of this discussion is that spectroscopic studies on relevant small molecule model compounds have been melded with analogous studies on the enzyme systems to arrive at a sophisticated description of active site electronic structure. As the field moves forward, it will become increasingly important to understand the structure, function and reaction mechanisms for the numerous non-canonical [ie. beyond sulfite oxidase, xanthine oxidase, DMSO reductase) pyranopterin Mo enzymes. 

Animal FASs are functional dimers [76]. While /3-ketoacyl synthase requires dimer formation for activity [77], catalysis of the remaining FAS reactions is carried out by the monomeric enzyme. This behavior is reminiscent of yeast fatty acid synthase, where the -ketoacyl synthase and ACP from different subunits also contribute to the same active site. Electron microscopy and small angle scattering experiments have further defined the structure of the functional complex [34,78]. The overall shape of the molecule, as visualized by electron microscopy, is two side by side cylinders with dimensions of 160x146 x 73 A [34]. 

Kennepohl P, Solomon El. 2003. Electronic structure contributions to electron-transfer reactivity in iron-sulfur active sites 3. Kinetics of electron transfer. Inorg Chem 42 696-708. 

Additional information has been obtained from single crystal, polarized optical and ESR spectroscopic studies924 on poplar plastocyanin, which have allowed a correlation of the electronic structure of the blue copper active site with its geometric structure. In summary, the three dominant absorption bands at 13 350, 16 490 and 17 870 cm-1 were assigned to CysS- Cu (d 2-,2 charge-transfer transitions. The methionine makes only a small contribution, due to the long Cu—S(Met) bond (2.9 A) and the poor overlap of the methionine sulfur orbitals with the dx y orbital of copper. Histidine-Cu charge transfer contributes to the weaker absorptions at 21 390 and... 

Fe(lll)> Fe(100)> Fe(110), with relative activities of 430 32 1 and for Re the order is Re(1120)> Re (1010 > Re (0001), with Re (1120) more than 1000 times more active than Re (0001). For both metals it is proposed that the active site is a metal atom in the second layer of an open surface structure, i.e., an atom in the bulk (having a high density of electron holes near the Fermi level) which is accessible to a gaseous molecule because of the open structure of the surface. This model emphasizes the unique electronic rather than structural sensitivity of this reaction. It is possible that similar electronic effects may contribute to structure sensitivity for other reactions (c.f. skeletal isomerization reactions, see later). 

Molybdopterin has another function besides participating in electron transfer between the site of catalysis and other electron-acceptor groups. It serves as an anchor for the active site where a multitude of hydrogen bonds between the pterin (and, if present, the dinucleotide) and the protein provide a secure tether for the reactive metal site (17). Evidence for the immobility conferred by the pterin(s) embedded in the protein is found in a comparsion of the DMSOR structures from both Rhodobacter sources. Regardless of the Mo coordination environment, the MGD ligands are nearly superimposable (75). This similarity of pterin structure is most clearly observed in the 1.3-A structure, where the Mo atom dissociated and shifted away from one pterin ligand, which otherwise was unaffected. The nucleotide tails on MGD, MCD, and other derivatives of molybdopterin also contribute to locking the molybdenum catalyst in position. 

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