Biochemistry active site

Plotnick, M. L, Mayne, L., Schechter, N. M., and Rnbiii, H., 1996. Distortion of the active site of chymotrypsin complexed widi a serpin. Biochemistry 35 7586-7590. 

Inhibitors must possess chemical and physical properties that will ensure absorption by root tips or penetration by foliar surfaces, and translocation to the active site. Once there they must assume the precise spatial configuration required to complement the molecular architecture of the active center if they are to block the key reaction. A comprehension of comparative biochemistry and information on how plants differ in the architecture of the reactive sites should assist in developing truly selective herbicides. 

Watson JN, Dookhun V, Borgford TJ, Bennet AJ (2003) Mutagenesis of the conserved active-site tyrosine changes a retaining sialidase into an inverting sialidase. Biochemistry 42 12682-12690... 

Chaudiere, J. and Tappel, A.L. (1984) Interaction of gold(I) with the active site of selenium-glutathione peroxidase. Journal of Inorganic Biochemistry, 20, 313—325. 

Lee, C.-H. Skibo, E. B. Active site directed reductive alkylation of xanthine oxidase by imidazo[4,5-g]quinazoline-4,9-diones functionalized with a leaving group. Biochemistry 1987, 26, 7355-7362. 

In the end, what is unique about computational methods is their ability to describe transition states and intermediates. This is why the calculation of reaction mechanisms has achieved such a prominent position in quantum biochemistry. We will therefore spend a considerable amount of time to describe when improved active-site geometries can be expected to give important beneficial effects on reaction energies. In addition, we will try to describe how the non-bonded interactions between active site and surrounding protein affect relative energies. 

Dillet V, Dyson HJ, Bashford D (1998) Calculations of electrostatic interactions and pKas in the active site of Escherichia coli thioredoxin. Biochemistry 37 10298-10306. 

Ciotti, M. and Owens, I.S. (1996) Evidence for overlapping active sites for 17 -ethynlestradiol and bilirubin in the human major bilirubin UDPglucuronosyltransferase. Biochemistry, 35, 10119—10124. 

Iverson, T. M., Alber, B. E., Kisker, C., Ferry, J. G., and Rees, D. C. (2000). A closer look at the active site of gamma-class carbonic anhydrases High-resolution crystallographic studies of the carbonic anhydrase from Methanosarcina thermophila. Biochemistry 39, 9222-9231. 

Larsen, T.M., Wedeking, J.E., Rayment, I. and Reed, G.H. (1996) A carboxylate oxygen of the substrate bridges the magnesium ions at the active site of enolase structure of the yeast enzyme complexed with the equilibrium mixture of 2-phosphoglycerate and phosphoenolpyruvate at 1.8 A resolution, Biochemistry, 30, 4349-4358. 

We begin this overview of manganese biochemistry with a brief account of its role in the detoxification of free radicals, before considering the function of a dinuclear Mn(II) active site in the important eukaryotic urea cycle enzyme arginase. We then pass in review a few microbial Mn-containing enzymes involved in intermediary metabolism, and conclude with the very exciting recent results on the structure and function of the catalytic manganese cluster involved in the photosynthetic oxidation of water. 

Schrag, M.L. and Wienkers, L.C. (2001) Covalent alteration of the CYP3A4 active site evidence for multiple substrate binding domains. Archives of Biochemistry and Biophysics, 391 (1), 49-55. 

Korzekwa, K.R., Krishnamachary, N., Shou, M., Ogai, A., Parise, R.A., Rettie, A.E., Gonzalez, F.J. and Tracy, T.S. (1998) Evaluation of atypical cytochrome P450 kinetics with two-substrate models evidence that multiple substrates can simultaneously bind to cytochrome P450 active sites. Biochemistry, 37 (12), 4137-4147. 

Magnetic resonance techniques have again been popular for studying enzymes which are involved in phosphate hydrolysis and transfer. 31P or 19F N.m.r.1-2 and spinlabelling3 have all been used to study the interaction of substrates with these enzymes, while affinity labelling4 5 6 7 is another technique which has been used to obtain information about the sequence and conformation of amino-acid chains at the active sites of enzymes. Recently, these experimental methods have been applied to the study of cell membranes,6-7 and these are mentioned in a new series of books concerned with enzymes in biological membranes.8 A new journal, Trends in Biochemical Sciences, which contains concise, up-to-date reviews on these and other topics is published by Elsevier on behalf of the International Union of Biochemistry. 

T. C. M. Eames, R. M. Pollack, and R. F. Steiner, Orientation, accessibility, and mobility of equilenin bound to the active site of steroid isomerase, Biochemistry 28, 6269-6275 (1989). 

In the equations describing enzyme kinetics in this chapter, the notation varies a bit from other chapters. Thus v is accepted in the biochemical literature as the symbol for reaction rate while Vmax is used for the maximum rate. Furthermore, for simplification frequently Vmax is truncated to V in complex formulas (see Equations 11.28 and 11.29). Although at first glance inconsistent, these symbols are familiar to students of biochemistry and related areas. The square brackets indicate concentrations. Vmax expresses the upper limit of the rate of the enzyme reaction. It is the product of the rate constant k3, also called the turnover number, and the total enzyme concentration, [E]o. The case u, = Vmax corresponds to complete saturation of all active sites. The other kinetic limit, = (Vmax/KM)[S], corresponds to Km >> [S], in other words Vmax/KM is the first order rate constant found when the substrate concentration approaches zero ... 

A. Purohit, G. J. Williams, N. M. Howarth, B. V. L. Potter, M. J. Reed, Inactivation of Steroid Sulfatase by an Active Site-Directed Inhibitor, Estrone-3-O-sulfamate , Biochemistry 1995, 34, 11508- 11514. 

M. J. Muller, B. Samuelsson, J. Z. Haeggstrom, Chemical Modification of Leukotriene A4 Hydrolase. Indications for Essential Tyrosyl and Arginyl Residues at the Active Site , Biochemistry 1995, 34, 3536 - 3543. 

Francisco, W.A., Blackburn, N.J. and Klinman, J.P. (2003). Oxygen and hydrogen isotope effects in an active site tyrosine to phenylalanine mutant of peptidylglycine alpha-hydroxylating monooxygenase mechanistic implications. Biochemistry 42, 1813-1819... 

Lemon, B. J. and Peters, J. W. (1999) Binding of exogenously added carbon monoxide at the active site of the iron-only hydrogenase (CpI) from Clostridium pasteurianum. Biochemistry, 38, 12969-73. 

Massanz, C. and Friedrich, B. (1999) Amino acid replacements at the H(2)-activating site of the NAD-reducing hydrogenase from Alcaligenes eutrophus. Biochemistry, 38, 14330-7. 

Bennett B, Lemon BJ, Peters JW. 2000. Reversible carbon monoxide binding and inhibition at the active site of the Fe-only hydrogenase. Biochemistry 39 7455-60. 

Figure 11.3. The active site of Cab. Reprinted with permission from Strop et al. (2001), copyright 2001 American Society for Biochemistry and Molecular Biology.

Nolle, H. J. Rosenberry, T. L. Neumann, E. Effective charge on acetylcholinesterase active sites determined from the ionic strength dependence of association rate constants with cationic ligands. Biochemistry 1980, 19, 3705-3711. 

Kobayashi, Y., Fang, X., Szklarz, G. D., and Halpert, J. R. (1998) Probing the active site of cytochrome P450 2B1 metabolism of 7- alkoxycoumarins by the wild type and five site-directed mutants. Biochemistry 37, 6679-6688. 

Shou, M., Grogan, J., Mancewicz, J. A., et al. (1994) Activation of CYP3A4 Evidence for the simultaneous binding of two substrates in a cytochrome P450 active site. Biochemistry 33, 6450-6455. 

M. R. Sierks, K. Bock, S. Refn, and B. Svensson, Active site similarities of glucose dehydrogenase, glucose oxidase, and glucoamylase probed by deoxygenated substrates, Biochemistry, 31 (1992) 8972-8977. 

F. Naider, Z. Bohak, and J. Yariv, Reversible alkylation of a methionyl residue near die active site of p-galactosidase, Biochemistry, 11 (1972) 3202—3207. 

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