Cofactor proteins

Iron constituent of cytochromes and other heme or nonheme proteins cofactor for a number of enzymes. 

Shimomura, O., and Johnson, F. H. (1968c). Purification and properties of the luciferase and of a protein cofactor in the bioluminescence system of Latia neritoides. Biochemistry 7 2574-2580. 

Protein (cofactor) (assigned amino acids) % H assignment NOE Ri Fe-Sy-C)3-C dihedral angle mean (A) Number of conformers PDB entry... 

The heme moiety provides de novo designed heme proteins with an intrinsic and spectroscopically rich probe. The interaction of the amide bonds of the peptide or protein with the heme macrocycle provides for an induced circular dichroism spectrum indicative of protein-cofactor interactions. The strong optical properties of the heme macrocycle also make it suitable for resonance Raman spectroscopy. Aside from the heme macrocycle, the encapsulated metal ion itself provides a spectroscopic probe into its electronic structure via EPR spectroscopy and electrochemistry. These spectroscopic and electrochemical tools provide a strong quantitative base for the detailed evaluation of the relative successes of de novo heme proteins. 

SOLUBILITY PRODUCT IRON-SULFUR CLUSTER Iron-sulfur protein cofactors,... 

Current available information does not permit definitive conclusions on the nature, specificity, and mechanism of action of the protein cofactor (s) of lipoprotein lipase. It is verj difiicult to correlate the observations described above (summarized in Table 10) since the enzyme preparations used were not pure or well characterized, and were derived from various sources. For instance, two species of lipoprotein lipase have been reported to exist in rat adipose tissue (G4), and major differences between enzymes of liver and adipose tissue have been noted (G16). Also, the nature of the apoprotein preparations employed as protein cofactor (s) of lipoprotein lipase has not been clearly specified in all the studies contaminated materials may account for the spurious results observed. At present, it is not known how apoproteins such as apo Glu, apo Ala, and apo Ser could exhibit their activator or inhibitor activity on lipoprotein lipase. If these different apoproteins indeed prove to be cofactors for lipoprotein lipase, the nature of the lipid-protein specificity must be established and thus the role played by carbohydrates, since some of these apoproteins are glycoproteins. 

In addition to a serum protein cofactor, calcium has been shown to be necessary for attainment of maximal reaction rates of partially purified... 

Protein C functions as an anticoagulant by proteolytically inactivating two protein cofactors of blood coagulation, factors V and VIII.402 It too circulates in a zymogen form and is activated by limited proteolysis. Protein C appears to contain about 16 sites for Ca2+, all of equal affinity, while activated protein C binds about nine Ca2+. Conformational rearrangement during activation results in loss of binding sites. 

The MPMV CTE is distinct from the HIV-1 RRE in that it must rely on a cellular protein cofactor to function. The next step was to identify this cofactor. Competition and inhibitor experiments revealed that CTE is not dependent on CRM1 nuclear export factor (Bogerd et al., 1998 Otero et al., 1998 Pasquinelli et al., 1997a Saavedra et al., 1997). In addition, microinjection of high levels of CTE in Xenopus oocyte nuclei selectively inhibited mRNA export, while tRNA, U snRNA, and Rev-RRE-dependent RNA export were unaffected (Pasquinelli et al., 1997a Saavedra et al., 1997). Thus, the CTE cofactor was also likely to be a key participant in cellular mRNA export. 

Catalytic antibodies, predicted by Jencks in 1969 and first discovered in 1986, can now be raised against a wide variety of haptens covering nearly every reaction. Catalytic antibodies are regarded as the best enzyme mimics, with very good selectivity, but almost always their catalytic efficiency is by far insufficient. Some natural RNA molecules act as catalysts with intrinsic enzyme-like activity which permits them to catalyze chemical reactions in the complete absence of protein cofactors. In addition, ribozymes identified through in-vitro selection have extended the repertoire of RNA catalysis. This versatility has lent credence to the idea that RNA molecules may have been central to the early stages of life on Earth. 

These reactive metabolites can bind covalently to cellular macromolecules such as nucleic acids, proteins, cofactors, lipids, and polysaccharides, thereby changing their biologic properties. The liver is particularly vulnerable to toxicity produced by reactive metabolites because it is the major site of xenobiotic metabolism. Most activation reactions are catalyzed by the cytochrome P450 enzymes, and agents that induce these enzymes, such as phenobarbital and 3-methylcholanthrene, often increase toxicity. Conversely, inhibitors of cytochrome P450, such as SKF-525A and piperonyl butoxide, frequently decrease toxicity. 

Unfortunately, the one x-ray structure of a coenzyme B -dependent enzyme reported has disorder problems and has a mixture of forms of the cofactor thus, it is difficult to discern well the role of the protein [33]. The evidence that protein-cofactor contacts are important in the activation process is limited almost exclusively to a few of the coenzyme B 12-dependent enzymes. This evidence will be discussed later. 

Nonblue. These include galactose oxidase (GO) and amine oxidases (e.g., plasma amine oxidase, diamine oxidase, lysyl oxidase), which produce dihydrogen peroxide by the two-electron reduction of 02 [33], For GO (stereospecific primary alcohol oxidation), spectroscopic studies by Whittaker [70,71] suggest that the two-electron oxidation carried out by a mononuclear copper center is aided by a stabilized ligand-protein radical (i.e., (L)Cu(I) + 02 —> (L +)Cu(lI) + H202), obviating the need to get to Cu(III) in the catalytic cycle. Protein x-ray structures [33,72] reveal a novel copper protein cofactor, which would seem... 

Fielding CJ, Shore VG, Fielding PE. A protein cofactor of lecithin Cholesteryl acyl-transferase. Biochem Biophys Res Commun. 1972,46 1493-1498. 

Photoswitchable sub strate-protein / cofactor- enzyme/antigen-antibody interactions Light-stimulated affinity chromatography Immobilization of photoactive separation component on solid matrices... 

Allen, J. P., Feher, G., Yeates, T. O., Komiya, H., and Rees, D. C., 1988, Structure of the reaction center from Rhodobacter sphaeroides R-26 Protein-cofactor (quinones and Fe interactions. Proc. Natl. Acad. Sci. USA, 85 849798491. 

Ermler, U., Eritzsch, G., Buchanan, S. K., and Michel, H., 1994a, Structure of the photosynthetic reaction centre from Rhodobacter sphaeroides at 2.65 resolution Cofactors and protein-cofactor interactions. Structure, 2 9259936. 

Because of the rapid decay of the electronic coupling with distance, very long-distance (>40 A) ET reactions rarely occur in a single step. Instead, extremely long range ET involves an array of multiple redox centers, mobile electron carriers, or large-scale motion of redox-active domains (46). All intermolecular ET reactions require either protein-protein docking or formation of an encounter complex in which the two protein cofactors are... 

SPP seems to be less complicated than y-secretase. The expression of human SPP in yeast reconstituted the protease activity, which suggests that the protein has activity on its own and does not require other mammahan protein cofactors (72). Moreover, unhke presenilins, SPP is not processed into two pieces. Thus, SPP may be a more tractable enzyme for understanding this type of intramembrane aspartyl protease and may shed light on y-secretase structure and function. Indeed, the catalytic sites of the two proteases seem remarkably similar their activities... 

---