Modular enzymes

It has to be said that all of the mentioned complications should be considered exceptions rather than the rule. Overall, an analysis of conservation patterns has been and will continue to be a valuable tool in the identification and classification of new enzyme families. 

A survey of known three-dimensional structure of proteins shows that a sizeable portion of them contain several apparently independent folding units, usually referred to as domains . 

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Burgdorf T, Lenz O, Buhrke T, van der Linden E, Jones AK, Albracht SPJ, Friedrich B. 2005. [NiFe]-hydrogenases of Rahtonia eutropha H16 Modular enzymes for oxygen-tolerant biological hydrogen oxidation. J Mol Microbiol Biotechnol 10 181-196. 

There are at least three types of PKS. Type I PKSs catalyze the biosynthesis of macrolides such as erythromycin and rapamycin. As modular enzymes, they contain separate catalytic modules for each reaction catalyzed sequentially in the polyketide biosynthetic pathway. Type II PKSs have only a few active sites on separate polypeptides, and the active sites are used iteratively, catalyzing the biosynthesis of bacterial aromatic polyketides. Type III are fungal PKSs they are hybrids of type I and type II PKSs [49,50]. 

CE Family 1 is very large and contains members which do not act on carbohydrate-derived substrates. The crystal structure of a CE 1 domain of XynlOB modular enzyme from Clostridium thermocellum has been solved. " The CE 1 domain is a feruloyl esterase which hydrolyses the feruloyl groups attached to some arabinofuranosyl 05 groups in native xylan. (The Xyn lOB protein as a whole consists of two CBM 22 domains, a dockerin domain, and a GH 20 xylanase domain, and forms part of a cellulosome - see Section 5.10.) The enzyme has the common a/p hydrolase fold. Studies of ferulic acid complexes of the inactive alanine mutant of the active site serine revealed the classic catalytic triad, and two main-chain peptide NH bonds are in place to form an oxyanion hole . A remarkable feature is that the enzyme as repeatedly isolated was esterilied on the active site serine by phosphate or sulfate. 

Polyketides are a diverse class of compounds that are often created by a series of modular enzymes which condense and then modify chains of acetate or propionate units primarily through reduction, dehydration, cyclization, and aromatization reactions. Polyketides, with their enormous structural variety, show a broad range of biological activities (see Chapters 1.10 and 1.11). 

A modular architecture is no particular hallmark of enzymes, the highest degree of modularity is typically observed in structural proteins of the extracellular matrix and in proteins involved in intracellular signal transduction. Nevertheless, there are a number of modular enzymes including some which are of interest for biocatalytic applications. 

Chaitan Khosla and Pehr B. Harbury, Modular enzymes, Nature, 409 (2001), 247-252. 

Houslay M, Adams DR. PDE4 cAMP phosphodiesterases modular enzymes that orchestrate signaling cross-talk, desensitization, and compartmentalization. Biochem J 2003 370 1-18. 

Modular enzymes fall into three categories of modular catalysts ... 

Methionine synthase (MetH) of E. coli represents the most thoroughly studied B12-dependent methyl transferase and is one of the essential roles of B12 in mammalian metabolism [125,153,154]. It is a modular enzyme containing separate binding domains for homocysteine, N -methyltetrahydrofolate, S-adenosyl-methionine (SAM) and the Bi2-cofactor [125,153-155]. The B12-binding domain in its different oxidation states must interact punctually and specifically with each of the other three domains The Co(I) form with the N -methyltetrahydrofolate binding domain, the Co(II) form with the SAM binding domain, and the CH3 - Co (III) form with the homocysteine binding domain [153,155]. 

Modular enzyme kinetic equation buiiding 3.1 Unified modifier equation... 

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