Glyceraldehyde-3-phosphate dehydrogenase structure

Figure 2-13 (A) Stereoscopic view of the nucleotide binding domain of glyceraldehyde phosphate dehydrogenase. The enzyme is from Bacillus stearothermophilus but is homologous to the enzyme from animal sources. Residues are numbered 0-148. In this wire model all of the main chain C, O, and N atoms are shown but side chains have been omitted. The large central twisted P sheet, with strands roughly perpendicular to the page, is seen clearly hydrogen bonds are indicated by dashed lines. Helices are visible on both sides of the sheet. The coenzyme NAD+ is bound at the end of the P sheet toward the viewer. Note that the two phosphate groups in the center of the NAD+ are H-bonded to the N terminus of the helix beginning with RIO. From Skarzynski et al.llla (B) Structural formula for NAD+.

Zinc is essential for the functioning of at least twenty different enzymes, and their functions are widely varied. They include the alcohol dehydrogenases of yeast and mammalian liver, glyceraldehyde phosphate dehydrogenase, phosphoglycomutase of yeast, DNA and RNA polymerases (at least in bacteria), alkaline phosphatase in bacteria, mammalian carbo-xypeptidase, carbonic anhydrase, AMP hydrolase, pyruvate carboxylase (yeast), and aldolase (yeast and bacteria). The alkaline phosphatase of E, coli has, in each molecule, four atoms of zinc the two which maintain structure can be replaced by Mn, Co +, or Cu, whereas the other two atoms are essential for enzyme action (Trotman and Greenwood, 1971). 

FIGURE 6.34 Sheet structures formed from andparallel arrangements of /3-strands, (a) Streptomyces suh i x Xu inhibitor, (b) glutathione reductase domain 3, and (c) the second domain of glyceraldehyde-3-phosphate dehydrogenase represent minimal andparallel /S-sheet domain structures. In each of these cases, an andparallel /S-sheet is largely exposed to solvent on one face and covered by helices and random coils on the other face. (Jane Richardson)... 

Halophilic proteins whose solution structures are currently under study include glyceraldehyde-3-phosphate dehydrogenase from Hal-oarcula vallismortis (Krishnan and Altekar, 1990) and a heme-binding catalase-peroxidase from H.marismortui (F. Cendrin, H. Jouvre, and G. Zaccai, private communication). 

Glyceraldehyde-3-phosphate dehydrogenase has an essential cysteine residue in its active site. The enzyme forms a transient acyl compound with its substrate, glyceraldehyde 3-phosphate, (a) What is the general chemical name of the compound (b) Draw its likely structure. 

Fig. 23. Proposed active site arrangement of sn-glycerol-3-phosphate dehydrogenase (below), based on secondary structure predicted from the known primary structure, and on comparison with the known tertiary structure of glyceraldehyde-3-phosphate dehydrogenase (above). From the work of Rossmann and colleagues (94).

A similar conclusion was arrived at by Arnold and Pette ( 2) from studies carried out on the in vitro binding of aldolase glyceraldehyde phosphate dehyrogenase, fructose-6-phosphate kinase, phosphoglycerate kinase, pyruvate kinase and lactate dehydrogenase to the structural proteins F-actin, myosin, acto-myosin and stromaprotein. 

Water arrangements essentially similar to those for lysozyme have been found for various other high-resolution structures of proteins, for example, penicillopepsin (James and Sielecki, 1983), ferricytochrome c (Finzel et al., 1985), glyceraldehyde-3-phosphate dehydrogenase (Skar-zynski et al., 1987), and bacteriophage T4 lysozyme (Weaver tuid Matthews, 1987). Wlodawer et al. (1988) described the solvent about phosphate-free ribonuclease A, at 1.26 A, and have compared their results with those for other high-resolution structures of this protein. 

Figure 16.7. Structure of Glyceraldehyde 3-Phosphate Dehydrogenase. The active site includes a cysteine residue and a histidine residue adjacent to a hound NAD+. 

T. Skarzynski, P C. Moody, and A.J. Wonacott. 1987. Structure of holo-glyceraldehyde-3-phosphate dehydrogenase homBacillus stearothermophilus at 1.8 A resolution J. Mol. Biol. 193 171-187. (PuhMed)... 

It is not the purpose of this review to provide a comprehensive account of these structure-function studies however, the case of citrate synthase will be described briefly to illustrate the potential of such investigations. The studies on malate dehydrogenase are reviewed by Eisenberg et al. [81], and those on glyceraldehyde 3-phosphate dehydrogenase are described in detail in Chapter 7. 

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