Cofactors structure

Figure 2. Pharmacofamilies of the NADH cofactor (structure shown in panel A) binding to oxi-doreductases. Panel B shows an overlay of a subset of NAD(P)(H) geometries obtained from 288 crystal structures of oxidoreductases. The two largest pharmacofamilies are shown, corresponding to the two-domain Rossmann fold enzymes in pharmacofamilies 1 (anti) and 2 (syn). Panel C shows the corresponding pharmacophores with all protein heteroatoms indicated that are within hydrogen bonding distance of atoms in the cofactor. (Figure adapted with permission from original work of Sem ef o/. ).

The FeMo-cofactor structure can be viewed as the assembly of two incomplete... 

The structure of PYP is known to 0.1 nm resolution (Fig. 23-47).601607 Structures have also been determined for a very early intermediate by trapping at -100°C607 and for Ij (pR). The cofactor structures are shown in Eq. 

Figure 2 The structures ofthe MPT cofactor subfamilies. The boxes represent subfamilies of molybdenum and tungsten enzymes with high sequence homology. Cofactor structure type determined aby x-ray crystallography from the listed source bby EXAFS.

The unique structure of the FeMoco has provided a challenge for synthetic chemists. Indeed it is difficult to envisage how such a molecular assembly can be constructed in situ. The current approach is to prepare synthetic analogs of fragments of the cofactor structure and to explore their reactivities. 

Examination of the cofactor structure shows that the six central, 3-coordinate, Fe centers are best described as trigonal pyramidal rather than trigonal planar,... 

Wamcke, K., and Dutton, P. L., 1993, Influence of QA site redox cofactor structure on equilibrium binding, in situ electrochemistry, and electron transfer performance in the photosynthetic reaction center protein Biochemistry 32 4769n4779. 

This book is one of the best known overall testaments of enzyme chemistry. It covers measurements, preparation, kinetics, nomenclature, specificity, mechanisms, inhibitors, cofactors, structures, biosynthesis, enzyme systems, and enzyme biology. In addition, a fairly broad list of classified enzymes and crystallized enzymes is appendicized. The book... 

Enzymatic cofactors, such as nicotinamide adenine dinucleotide (NADH), nicotinamide adenine dinucleotide phosphate (NADPH), flavin adenine dinucleotide (EAD), flavin mononucleotide (EMN), and pyridoxal phosphate, are fluorescent and commonly found associated with various proteins where they are responsible for electron transport (see Fig. lb and Table 1). NADH and NADPH in the oxidized form are nonfluorescent, whereas conversely the flavins, FAD and EMN, are fluorescent only in the oxidized form. Both NADH and FAD fluorescence is quenched by the adenine found within their cofactor structures, whereas NADH-based cofactors generally remain fluorescent when interacting with protein structures. The fluorescence of these cofactors is often used to study the cofactors interaction with proteins as well as with related enzymatic kinetics (1, 9-12). However, their complex fluorescent characteristics have not led to widespread applications beyond their own intrinsic function. 

Figure 5.2 Enzyme cofactor structures and redox processes for (a) FAD/FADH2, (b) NAD / NADH, and (c) PQQ. R represents adenosine diphosphate.

Figure 17.7. Chain of residues important for hydride transfer in E.coli DHFR. Substrate and cofactor structures are in red and green respectively with dot surfaces. Blue balls with adjacent numbering denote residue location. (Reproduced from Ref [38].)...

Figure 1 Iron-molybdenum cofactor structures in resting (left) and hypothetical dinitrogen-bound states (right)...

This chapter gives an overview of the biosynthesis of THF, (6if)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4), and molybdopterin (MPT), the organic compound of the molybdenum cofactor (Moco), and discusses the enzymoiogy of the proteins that bind the three classes of cofactors (structures are shown in Scheme 1). The biosynthesis of THF, BH4, and MPT start from guanosine triphosphate (GTP), but the reactions for the conversion of GTP into the three cofactors are diverse and involve different enzymatic compounds. 

From the cofactor structure, we now know that the thiol sulfurs are not directly connected to the pterin ring rather, they are appended from the pyran ring. Therefore, formation of urothione from the molybdenum cofactor must involve a cyclization step, and a similar process may also be involved in the formation of form B (1). Such reactions have been modeled through oxidation of quinoxaline dithiolene ligand (Scheme 2.29) as well as in complexes (see Scheme 2.20 above). ... 

J. L. Johnson, B. E. Mainline, K. V. Rajagopalan and B. H. Arison, The Pterin Component of the Molybdenum Cofactor Structural characterization of two fluorescent derivatives,/ Biol Chem., 1984,259, 5414-5422. 

Finally, we must consider how protons are delivered to complete the reaction. Without definitive evidence, molecular modeling has identified three likely proton-transfer routes (71). One is the interstitial channel, filled with water molecules, that nms between the a- and )3-subunits from the surface of the MoFe protein to the pool of water molecules around the homocitrate of the FeMo-cofactor. This channel could deliver protons rapidly to boimd substrate and might also provide a pathway for N2 and NH4+ to enter and leave the reduction site (see also the section Substrate-Binding Site). Extensive theoretical studies of the hydrogen-related chemistry of the FeMo-cofactor use this same interstitial channel to deliver protons (75). These studies indicate that the delivery of electrons to the FeMo-cofactor causes its sulfur atoms to become more basic which, in turn, makes them attractive sites for protonation by water molecules in the interstitial pool. Once transferred, these protons become reduced to hydrogen atoms that can then migrate across the FeMo-cofactor structure to other Fe and S atoms and become involved in substrate reduction (76). 

Figure 2 Cofactor structure of RC from Rb. Sphaeroides. In this figure, chromophores along the L and M branches are indicated by A and B, respectively. (Reprodnced with permission from Ref. 7. J. P. Allen et al., 1987.)...

Effect of Cofactor Structure on Control of Electron Transfer Rates at the Site of the Reaction Center Protein... 

The following generalized rate expression, derived from Fermi s golden rule (see e.g., [9,11]), is useful for discussing the effects of cofactor structure changes on the electron transfer rate constant (kgj) ... 

---