Big Chemical Encyclopedia

Chemical substances, components, reactions, process design ...

Articles Figures Tables About

Enoyl-reductase

All polyketides use the same general mechanism for chain elongation. Acetyl coenzyme A provides acetate (C2) units, which are condensed by a ketosynthase (KS). This in turn catalyzes condensation of the growing chain onto an acyl carrier protein (ACP), as generalized in Fig. 1.4. Enzymes such as ketoreductase (KR), enoyl reductase (ER), and dehydratase (DH) establish the oxidation state of caibon during translation, imparting structural diversity. Successive translation of each module leads to a chain of the required length that is eventually passed to thioeste-rase (TE), which releases the chain as a free acid or lactone. [Pg.10]

Scheme 23 Example of an acyl carrier protein (ACP in red) in a type I FAS. The palmitic acid is depicted as a representative fatty acid. During its biosynthesis, the ACP (red) interacts iteratively with each domain (DH, dehydrogenase ER, enoyl reductase KR, ketoreductase KS, ketosynthase TE, thioesterase) until the palmitic acid has reached its proper length. Scheme 23 Example of an acyl carrier protein (ACP in red) in a type I FAS. The palmitic acid is depicted as a representative fatty acid. During its biosynthesis, the ACP (red) interacts iteratively with each domain (DH, dehydrogenase ER, enoyl reductase KR, ketoreductase KS, ketosynthase TE, thioesterase) until the palmitic acid has reached its proper length.
Figure 11.5 Reactions of the fatty acid synthase complex. A single multi-subunit enzyme is responsible for the conversion of acetyl-CoA to palmitate. The subunits in the enzyme are (i) acetyltransferase, (ii) malonyltransferase, (iii) oxoacyl synthase, (iv) oxoacyl reductase, (v) hydroxyacyl dehydratase, (vi) enoyl reductase. Finally, a separate enzyme, thioester hydrolase, hydrolyses palmitoyl-CoA to produce palmitate (vii). Figure 11.5 Reactions of the fatty acid synthase complex. A single multi-subunit enzyme is responsible for the conversion of acetyl-CoA to palmitate. The subunits in the enzyme are (i) acetyltransferase, (ii) malonyltransferase, (iii) oxoacyl synthase, (iv) oxoacyl reductase, (v) hydroxyacyl dehydratase, (vi) enoyl reductase. Finally, a separate enzyme, thioester hydrolase, hydrolyses palmitoyl-CoA to produce palmitate (vii).
Acyl-CoA dehydrogenases (Flavin) Succinic dehydrogenase (Flavin) Opposite enoyl reductase (NADPH)... [Pg.766]

Enoyl-acyl carrier protein reductase 777 Enoyl hydratase 681 Enoyl reductase 766... [Pg.915]

Although isoniazid has been in use for about 45 years, the enzyme that it inhibits has been recognized only recently. It is a specific NADH-depen-dent enoyl reductase involved in synthesis of mycolic acids.h/1 The isoniazid must be activated by action of a bacterial catalase-peroxidaseh This enzyme may convert the drug to a reactive radical that combines with a NADH-derived radical to form an adduct in the active site of the enzymes. One possible reaction sequence follows.11 However, the mechanisms are not clear. [Pg.1194]

ACP acyl carrier protein AT acyltransferase DH dehydratase ER enoyl reductase KR p-ketoacyl reductase KS p-ketoacyl synthase TE thioesterase... [Pg.115]

Figure 3 The fatty acid biosynthetic cycle (ACP, acyl carrier protein KS, P-ketoacyl synthase KR, P-ketoacyl reductase DH, dehydratase ER, enoyl reductase TE, thioes-terase). Figure 3 The fatty acid biosynthetic cycle (ACP, acyl carrier protein KS, P-ketoacyl synthase KR, P-ketoacyl reductase DH, dehydratase ER, enoyl reductase TE, thioes-terase).
Figure 5 Domain organization of the erythromycin polyketide synthase. Putative domains are represented as circles and the structural residues are ignored. Each module incorporates the essential KS, AT, and ACP domains, while all but one include optional reductive activities. AT, acyltransferase ACP, acyl carrier protein KS, (3-ketoacyl synthase KR, P-ketoacyl reductase DH, dehydratase ER, enoyl reductase TE, thioesterase. Figure 5 Domain organization of the erythromycin polyketide synthase. Putative domains are represented as circles and the structural residues are ignored. Each module incorporates the essential KS, AT, and ACP domains, while all but one include optional reductive activities. AT, acyltransferase ACP, acyl carrier protein KS, (3-ketoacyl synthase KR, P-ketoacyl reductase DH, dehydratase ER, enoyl reductase TE, thioesterase.
FIGURE 19.4 Modular organization of the six modules (I—VI) of 6-deoxyerythronolide B synthase (DEBS) enzyme as derived from Saccharopolyspora erythraea. Enzyme activities are acyltransferases (AT), acyl carrier proteins (ACP), fi-ketoacyl-ACP synthases (KS), P-ketoreductases (KR), dehytratases (DH), enoyl reductases (ER), and thioesterases (TE). The TE-catalyzed release of the polyketide chain results in the formation of 6-dEB (70), 375 379 383... [Pg.389]

Xu H, Sullivan TJ, Sekiguchi J et al (2008) Mechanism and inhibition of saFabl, the enoyl reductase from Staphylococcus aureus. Biochemistry 47 4228-4236... [Pg.259]

Figure 19.13 Biosynthesis of palmitate via fatty acid synthetase. The numbered enzyme activities (steps) are as follows (1) acetyl-CoA transacylase (2) malonyl-coA transacylase (3) /3-ketoacylsynthetase (4) j3-ketoacylreductase (5) /3-hydroxyacyldehydratase (6) enoyl reductase (7) fatty acyltransacylase. (Reproduced by permission from Wakil SJ, Stoops JK, Joshi VC. Fatty acid synthesis and its regulation. Annu Rev Biochem 52 537-579, 1983.)... Figure 19.13 Biosynthesis of palmitate via fatty acid synthetase. The numbered enzyme activities (steps) are as follows (1) acetyl-CoA transacylase (2) malonyl-coA transacylase (3) /3-ketoacylsynthetase (4) j3-ketoacylreductase (5) /3-hydroxyacyldehydratase (6) enoyl reductase (7) fatty acyltransacylase. (Reproduced by permission from Wakil SJ, Stoops JK, Joshi VC. Fatty acid synthesis and its regulation. Annu Rev Biochem 52 537-579, 1983.)...
The animal fatty acid synthase (FAS EC 2.3.1.85) is one of the most complex multifunctional enzymes that have been characterized, as this single polypeptide contains all the catalytic components required for a series of 37 sequential transactions (Smith, 1994). The animal FAS consists of two identical polypeptides of approximately 2500 amino acid residues (MW, ca. 270 kDa), each containing seven catalytic subunits (1) ketoacylsynthase, (2) malonyl/acetyl transferase, (3) dehydrase, (4) enoyl reductase, (5) (3-kcto reductase, (6) acyl carrier protein (ACP), and (7) thioesterase. Although some components of the complex are able to carry out their respective catalytic steps in the monomeric form, only in the FAS dimer do the subunits attain conformations that facilitate coupling of the individual reactions of fatty acid synthesis to occur (Smith et al., 2003). [Pg.58]

Cavies, camels Alcohol dehydrogenases, enoyl reductases... [Pg.566]

AT = acyl transferase DH = dehydratase ER = enoyl reductase KR = ketoreductase KS = ketosynthase mAT = methylmalonyl-specific acyl transferase. [Pg.303]

Figure 10.2 The PKS/NRPS biosynthetic paradigm, showing the most common domains and their relative positions within a modular PKS/NRPS enzyme. A = adenylation AT = acyl transferase C = condensation DH = dehydratase Ep = epimerase ER = enoyl reductase KR = ketoreductase KS = ketosynthase MT = methyltransferase PCP = peptidyl carrier protein TE = thioesterase. Figure 10.2 The PKS/NRPS biosynthetic paradigm, showing the most common domains and their relative positions within a modular PKS/NRPS enzyme. A = adenylation AT = acyl transferase C = condensation DH = dehydratase Ep = epimerase ER = enoyl reductase KR = ketoreductase KS = ketosynthase MT = methyltransferase PCP = peptidyl carrier protein TE = thioesterase.
The )9-ketoacyl-synthases/acyltransferases (KS/ AT) in each module effect the chain elongation by methyl-malonyl-coenzyme A units catalyzing a Claisen e.ster condensation followed by decarboxylation (Scheme 2). Subsequent domains are module-specific ketoreductases (KR), dehydratases (DH) or enoyl-reductases (ER), which regulate the functionalization of the newly prepared fi-oxoesters. The stepwise growing chain is picked up by an acyl-carrier protein (ACP). [Pg.345]

Modular PKS enzymes are responsible for the synthesis of a wide diversity of structures and seem to have more relaxed specificities in several of the enzymatic steps. Their enormous appeal for combinatorial purposes, though, derives from the presence of multiple modules that can be manipulated independently, allowing the production of rings of different sizes and with potential stereochemical variation at each PK carbon. The higher complexity of these pathways has somewhat hindered their exploitation, but recently, several have been fully characterized. Among them, by far the most studied modular multienzyme complex is 6-deoxyerythronolide B synthase (DEBS 240,266,267), which produces the 14-member macrolide 6-deoxyerythronolide B (10.70, Fig. 10.45). DEBS contains three large subunits each of which contains two PKS enzyme modules. Each module contains the minimal PKS enzyme vide supra) and either none (M3), one (ketoreductase KR Ml, M2, MS, and M6), or three (dehydratase DH-enoyl reductase ER-ketoreductase KR, M4) catalytic activities that produce a keto (M3), an hydroxy (Ml, M2, MS and M6), or an unsubstituted methylene (M4) on the last monomeric unit of the growing chain (Fig. 10.45). A final thioesterase (TE) activity catalyzes lactone formation with concomitant release of 10.70 from the multienzyme complex. Introduction of TE activity after an upstream module allows various reduced-size macrolides (10.71-10.73, Eig. 10.45) to be obtained. [Pg.555]

Fig. 4. X-ray determined protein crystal structures of multienzyme ensembly lines, (a) Mammalian fatty acid synthase at 4.5 A resolution (PDB 2cf2). Domain organization A starter substrate, acetyl-CoA or malonyl-CoA, gets loaded onto the acyl-carrler protein (ACP/absent in the structure) via the malonyl-CoA-/acetyl-CoA-ACP transacylase (MAT). Then, the ketoacyl synthase (KS) catalyzes a decarboxylative condensation reaction and forms the B-ketoacyl-ACP. This is followed from a reduction reaction catalyzed by the B-ketoacyl reductase (KR). Subsequently, the Intermediate gets dehydrated by a dehydratase (DH) and additionally reduced by a B-enoyl reductase (ER). The product gets released from the ACP by a thloesterase (absent in the structure), (b) Module 3 of 6-deoxyerthronolide B synthase at 2.6 A resolution (PDB 2qo3) bound to the inhibitor cerulin. The ketosynthase (KS) - acyltransferase (AT) di-domain is part of the large homodimeric polypeptide involved in biosynthesis of erythromycin from Saccharopolyspora erythraea... Fig. 4. X-ray determined protein crystal structures of multienzyme ensembly lines, (a) Mammalian fatty acid synthase at 4.5 A resolution (PDB 2cf2). Domain organization A starter substrate, acetyl-CoA or malonyl-CoA, gets loaded onto the acyl-carrler protein (ACP/absent in the structure) via the malonyl-CoA-/acetyl-CoA-ACP transacylase (MAT). Then, the ketoacyl synthase (KS) catalyzes a decarboxylative condensation reaction and forms the B-ketoacyl-ACP. This is followed from a reduction reaction catalyzed by the B-ketoacyl reductase (KR). Subsequently, the Intermediate gets dehydrated by a dehydratase (DH) and additionally reduced by a B-enoyl reductase (ER). The product gets released from the ACP by a thloesterase (absent in the structure), (b) Module 3 of 6-deoxyerthronolide B synthase at 2.6 A resolution (PDB 2qo3) bound to the inhibitor cerulin. The ketosynthase (KS) - acyltransferase (AT) di-domain is part of the large homodimeric polypeptide involved in biosynthesis of erythromycin from Saccharopolyspora erythraea...
Once the hexameric structure of the yeast FAS was established, the number of functional active sites still remained to be determined. Earlier studies had shown that the functional complex contains approximately six equivalents each of two prosthetic groups 4 -phosphopantetheine [60,63], necessary for the AGP functionality, and flavin mononucleotide [64], an essential component of the enoyl reductase activity. These studies provided an early indication that each of the six active sites in the complex has a full set of the chemical groups necessary for fatty acid synthesis. Nevertheless, conflicting reports appeared in the literature as to the competence of six active sites. Whereas some reports suggested the possibility of half-sites reactivity (only three of the six sites are catalytically competent) [65, 66], others proposed that all six active sites could synthesize fatty acids [62]. Subsequent active site titration experiments were performed which quantitated the amount of fatty acyl products formed in the absence of turnover [67]. Single-turnover conditions were achieved through the use of... [Pg.94]

The seven activities of animal FASs are encoded as separate domains of a single 250 kDa polypeptide (Fig. 2) [30, 31]. These include a -ketoacyl synthase, malonyl/acetyl transferase, -ketoreductase, dehydratase, enoyl reductase, and an ACP domain with a phosphopantetheinylated serine. In addition to these activities, the animal FAS also includes a thioesterase domain which cleaves the product fatty acid from the enzyme. Proteolytic mapping of the polypeptide and genetic analysis have defined the location of the various domains in the primary sequence [30,31]. [Pg.96]

A series of uncompetitive inhibitors of InhA were developed using structure-based design from the crystal structure of tri-closan (4) bound to both coli enoyl reductase (called ecFabl)... [Pg.441]

Stewart MJ, Parikh S, Xiao G, Tonge PJ, Kisker C. Structural 46. basis and mechanism of enoyl reductase inhibition by triclosan. J. [Pg.453]

Figure 6 HMGS containing biosynthetic pathways. Portions of the PKS and PKS/NRPS pathways where the HMGS and related enzymes are located. Abbreviations A - Adenylation, AGP - acyl carrier protein, AT - acyltransferase, Cy - cyciization, DH - dehydratase, ER - enoyl reductase, GNAT -CCN5-related N-acetyltransferase, KS - ketosynthase, KR - ketoreductase, MT - methyltransferase. Ox - Oxidase, Oxy - Oxygenase, PGP - peptide carrier protein, PhyH - phytanoyl-CoA dioxygenase, PS - pyrone synthase, TE - thioesterase, - unknown function, - inactive domain. Figure 6 HMGS containing biosynthetic pathways. Portions of the PKS and PKS/NRPS pathways where the HMGS and related enzymes are located. Abbreviations A - Adenylation, AGP - acyl carrier protein, AT - acyltransferase, Cy - cyciization, DH - dehydratase, ER - enoyl reductase, GNAT -CCN5-related N-acetyltransferase, KS - ketosynthase, KR - ketoreductase, MT - methyltransferase. Ox - Oxidase, Oxy - Oxygenase, PGP - peptide carrier protein, PhyH - phytanoyl-CoA dioxygenase, PS - pyrone synthase, TE - thioesterase, - unknown function, - inactive domain.

See other pages where Enoyl-reductase is mentioned: [Pg.358]    [Pg.175]    [Pg.269]    [Pg.289]    [Pg.597]    [Pg.1187]    [Pg.37]    [Pg.18]    [Pg.156]    [Pg.433]    [Pg.257]    [Pg.60]    [Pg.572]    [Pg.377]    [Pg.422]    [Pg.302]    [Pg.93]    [Pg.93]    [Pg.97]    [Pg.240]    [Pg.440]    [Pg.453]    [Pg.1527]    [Pg.921]   
See also in sourсe #XX -- [ Pg.1194 ]

See also in sourсe #XX -- [ Pg.377 ]

See also in sourсe #XX -- [ Pg.766 ]

See also in sourсe #XX -- [ Pg.265 ]

See also in sourсe #XX -- [ Pg.1025 ]

See also in sourсe #XX -- [ Pg.672 , Pg.724 , Pg.1066 , Pg.1070 , Pg.1071 ]




SEARCH



2 - trans - Enoyl - CoA - reductase

Enoyl CoA reductase

Enoyl reductase domain, polyketide

Enoyl reductase domain, polyketide synthase

Enoyl-ACP reductase

Enoyl-acyl carrier protein reductase

© 2024 chempedia.info