Hexokinase, structural similarities

Figure 34.16. Actin and Hexokinase. A comparison of actin (blue) and hexokinase from yeast (red) reveals structural similarities indicative of homology. Both proteins have a deep cleft in which nucleotides bind. 

Two other commonly occurring hexoses which are usually found as components of polysaccharides or combined with other molecules in complex structures are galactose and fructose and, in a similar manner to other monosaccharides, enzymic methods are available for their measurement. An enzymic method for the measurement of fructose using hexokinase was described earlier, together with the method for mannose and glucose (Figure 9.22). 

A well-defined actin cytoskeleton is unique to eukaryotes prokaryotes lack such structures. How did filamentous actin evolve Comparison of the three-dimensional structure of G-actin with other proteins revealed remarkable similarity to several other proteins, including sugar kinases such as hexokinase (Figure 34.16 see also Section 16.1.1). 

A bilobal structure for each of the two monomers of hexokinase has also been reported (73). The similarity of hexokinase and PGK lobe structure suggests that these two enzymes have some similarity. 

Figures 4 and 5 illustrate the use of these shape descriptors. As a first example, we have considered two proteins with a similar number of amino acid residues but radically different folding patterns. Figure 4 contrasts the backbone of ribonudease inhibitor ( = 456) and yeast hexokinase ( = 457). These structures are found in the Brookhaven Protein Data Bank (PDB) with the codes IBNH and 2YHX, respectively. Ribonudease inhibitor is a very unusual horseshoe-shaped protein, the first known 3D structure of a protein with a highly repetitive amino acid sequence. Table 1 gives their size and entanglement characterization in terms of Rq, A, N, andN. Protem IBNH is less compact and less entangled than 2YHX (note the smaller N and N values).

TTie observation that kinases generally have a bilobal structure roughly similar to that found in hexokinase has led to the suggestion that analogous domain motions are a common feature of this class of enzymes. 

Sachsenheimer and Schulz report the structure of another crystalline form of adenylate kinase which appears to be related to the previously known form by a conformation change in a segment. The binding sites of ATP and AMP to this enzyme were also located. Similar work on the identification of binding sites and the assessment of conformational changes has been continued with ribo-nuclease, alcohol dehydrogenase, concanavalin A, " hexokinase, lysozyme," flavodoxin, and oxy-erythrocrurin." ... 

Enzymes differ from nonbiological catalysts in that they are specific for the substrate whose reaction they catalyze (Section 6.17). Enzymes, however, have different degrees of specificity. Some enzymes are specific for a single compound. Eor example, glucose-6-phosphate isomerase catalyzes the isomerization of glucose-6-phosphate only. On the other hand, some enzymes catalyze the reactions of several compounds with similar structures. Eor instance, hexokinase catalyzes the phosphorylation of any o-hexose. The specificity of an enzyme for its substrate is another example of molecular recognition— the ability of one molecule to recognize another molecule (Section 21.0). 

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