Aldose-ketose isomerases

L-Fucose isomerase catalyzes the interconversion of L-fucose to L-fuculose and o-arabinose to D-ribulose. It has neither sequence nor structural similarity with the other aldose-ketose isomerases. A crystal structure of the E. coli enzyme with an L-fucitol bound in the active site shows that the active site is located in a 20 A deep pocket, at the bottom of which is a single Mn ion. Mn is bound to Oi and O2 of L-fucitol the side chains of a monodentate Glu-337, a bidentate Asp-361 (with long bonds to both oxygens), His-528 and a water molecule. ... 

Creighton and Murthy recently reviewed the stereochemistry and related mechanistic issues associated with enzyme-catalyzed isomerizations that proceed by 1,2-hydrogen transfer or by 1,3-aUytic hydrogen transfer. In the first case, the prototypical aldose-ketose isomerase is triose-phosphate isomerase (or TPl), an enzyme that uses the carboxylate of Glu-165 as a base for abstracting a proton from the substrate during catalysis. A -3-Keto-... 

Demonstration that the enediol intermediate in aldose-ketose isomerase reactions is syn... 

As will be discussed in Chapter 16, the catalysis of a reaction by aldose-ketose isomerases involves an enediol intermediate in which the transferred proton (T in equation 8.18) remains on the same face of the intermediate. The stereochemistry of the products shows that the intermediate is syn rather than anti.9... 

Rose, I. A., Mechanism of the aldose-ketose isomerase reactions. Adv. Enz.ymol. 43 491, 1975. 

An enzymic counterpart of these complex base-catalysed rearrangements of sugars may be the reaction catalysed by 4-phospho-3,4-dihydroxy-2-butanone synthetase. The enzyme catalyses the formation of the eponymous intermediate in secondary metabolism from ribulose 5-phosphate. Labelling studies indicated that C1-C3 of the substrate became C1-C3 of the product, that H3 of the substrate derived from solvent and that C4 was lost as formate. X-ray crystal structures of the native enzyme and a partly active mutant in complex with the substrate are available. The active site of the enzyme from Met ha-nococcus jannaschii contains two metals, which can be any divalent cations of the approximate radius of Mg " or Mn ", the two usually observed. Their disposition is very reminiscent of those in the hydride transfer aldose-ketose isomerases, but also to ribulose-5-phosphate carboxylase, which works by an enolisation mechanism, so the enolisation route suggested by Steinbacher et al. is repeated in Figure 6.14, as is the Bilik-type alkyl group shift, for which an equivalent reverse aldol-aldol mechanism cannot be written. 

Other aldose/ketose isomerases with different substrate specificity have been cloned and overexpressedl86, including Fuc isomerase (Fuc I, EC 5.3.1.3) and Rha isomerase (Rha I, EC 5.3.1.14). Fuc isomerase, in combination with Fuc 1-P aldolase or Rha 1-P aldolase, has been used to prepare L-glucose, L-galactose, L-fucose, and derivatives from the corresponding L-glyceraldehyde derivatives and DHAP 87. ... 

Seemann and Schulz[2551 determined the three-dimensional structure of L-fucose isomerase from E. coli, a hexamer from a subunit with a molecular mass of 64 976 Da. The enzyme shows no structural similarity to any other aldose-ketose isomerases analyzed thus far. However, Seemann and Schulz, on the basis of the tertiary structure, suggested that the L-fucose isomerase reaction proceeds through an ene-diol intermediate [255l... 

The aldose-ketose isomerases constitute the best studied class of enzymes catalyzing 1,2-proton transfer reactions (Tables IV and V). Isomerization generally involves significant intramolecular hydrogen transfer with variable amounts of solvent proton exchange (16). This argues for the formation of an enediol(ate) intermediate facilitated by a single active site base partially shielded from solvent [Eq. (16)]. 

Aldose-Ketose Isomerases That Use (2R)-Aldoses as Substrates"... 

Glyoxalase I (lactoylglutathione lyase) has several stereochemical features in common with the aldose-ketose isomerases. This zinc metalloenzyme catalyzes the GSH-dependent conversion of a variety of aromatic and aliphatic a-ketoal-dehydes to their corresponding a-hydroxythio esters having the (7 )-configura-tion at C-2 (702, 103) [Eq. (21)] ... 

Thus, glyoxalase I may well conform to the stereochemical generalization first established for the aldose-ketose isomerases. 

Aldose-Ketose Isomerases.—The reactions catalysed by aldose-ketose isomerases, including proton-migration, stereochemical transformations, amination, and deamination, etc., have been reviewed. ... 

P-D-2-Acetamido-2-deoxy-hexosidase Acetylcholinesterase Adenosine 3, 5 -phosphate phosphodiesterase Aldose-ketose isomerases (general)... 

Now, finally, sedoheptulose 7-phosphate undergoes a transketolase-catalyzed (EC 2.2.1.2) process (as in Scheme 11.7) to remove two carbon atoms using the enzyme cofactor thiamine diphosphate to yield ribose 5-phosphate and a two-carbon fragment that has remained attached to the thiamine cofactor of transketo-lase (EC 2.2.1.1, sedoheptulose 7-phosphate) (Scheme 11.11). When the two-carbon fragment is added to glyceraldehyde 3-phosphate, the material of Scheme 11.8 again is applied and xylulose 5-phosphate results. The xylulose 5-phosphate isomerizes to ribulose 5-phosphate as in Scheme 11.9 (with intervention of ribulose phosphate 3-epimerase (EC 5.1.3.1). And, the ribose 5-phosphate, an aldose, isomerizes (an aldose-ketose isomerase, EC 5.3.1.6, ribose 5-phosphate isomerase) to ribulose 5-phosphate. 

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