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By Michael H. Anisfeld

This publication includes the English language texts of all GMPs (regulations, instructions, codes, and practices) carried out through nationwide and overseas regulatory professionals that govern the manufacture and checking out of biotechnology-derived items, lively pharmaceutical components, and prescription drugs. ready with the cooperation of wellbeing and fitness experts all over the world, this source comprises the GMPs in influence in 114 international locations, plus GMP laws of the area health and wellbeing association (including the 1996 WHO GMPs), the eu Union, the organization of South East Asian international locations, and the Pharmaceutical Inspection conference.

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6). It then reacts exergonically [60] via a transition state with a chairlike geometry [50]. The process appears to be concerted but asynchronous, with C±C bond formation lagging behind C±O bond cleavage [49]. The transition state for the enzymatic reaction has been shown to have a chairlike geometry as well [61], and conformationally constrained compounds that mimic this structure, such as the oxabicyclic dicarboxylic acid 1 (Fig. 6), are good inhibitors of chorismate mutase enzymes [62 ± 64].

Stadler, G. P. Wagner, W. Fontana, J. Theor. , 2002, in press. [53] A. D. Keefe, J. W. Szostak, Nature, 2001, 410, 715 ± 718. [54] J. Maynard Smith, Nature 1970, 225, 563 ± 564. [55] K. Yue, K. M. Fiebig, P. D. Thomas, H. S. Chan, E. I. Shakhnovich, K. A. Dill, Proc. Natl. Acad. Sci. USA, 1993, 90, 1942 ± 1946. [56] H. Li, R. Helling, C. Tang, N. Wingreen, Science, 1996, 273, 666 ± 669. [57] S. Govindarajan, R. A. Goldstein, Proc. Natl. Acad. Sci. USA, 1996, 93, 3341 ± 3345. [58] A. Babajide, I.

33 34 3 Using Evolutionary Strategies to Investigate the Structure and Function of Chorismate Mutases Fig. 3. Shikimate pathway for the biosynthesis of aromatic amino acids in plants and lower organisms. The [3,3]-sigmatropic rearrangement of chorismate into prephenate is shown in the box. PEP, phosphoenolpyruvate. The architectural diversity that nature exploits to promote this relatively simple chemical transformation is impressive and raises many intriguing questions. How do the individual enzymes work?

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