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On this page, you can see the structure of human salivary α-amylase. In general, α-amylase is an enzyme that catalyzes the hydrolysis of α-1,4 gulcan linkages in starch. It is found widely among all three kingdoms of life. The following will highlight important structural aspects related to the function of α-amylase. For more about the enzyme, click here.
Click here to reset and spin this α-amylase molecule.
Notice the α-helices highlighted in pink and the β-sheets highlighted in yellow. These are important secondary structural features of the enzyme that are characteristic of all α-amylases found in different organisms. Pay attention to the central eight-stranded parallel β-barrel, to one end of which are located the active site residues, which will be highlighted later. This structure appears to be conserved throughout most α-amylases across many domains. For more on the orthology of α-amylase, click here.
Click here to highlight the three different structural domains of the human α-amylase enzyme. Domain A (residues 1-99, 169-404) is highlighted in red, Domain B (residues 100-168) in green, and Domain C (residues 405-496) in purple. Domain A, the largest domain of the molecule, contains the central eight-stranded parallel β-barrel, highlighted previously. The active site residues located at one end of the barrel are also contained in Domain A, making it the most important domain of salivary α-amylase along with Domain B which houses most of the calcium ligand binding site to be highlighted next.
Here the ligands are highlighted that bind to this enzyme affecting its structure and function. α-Amylases in all organisms have been known to require at least one calcium ion per enzyme molecule for maintaining their tertiary structure and catalytic activity. It has also been found that the chloride binding site is specific to animal α-amylases. Notice that the calcium ligand is found directly between Domains A and B. Consequently, calcium plays a role in organizing the structure of Domain B. Also note the red unlabeled 'ligand' that appears. This is actually the N-terminal glutamine residue that undergoes a posttranslational modification to form a stable pyrrolidone derivative, pyroglutamic acid. It is thought that this modified amino acid residue may provide protection against other digestive enzymes.
Click here to highlight the active site amino acid residues Asp 197, Glu 233, and Asp 300 colored light pink. Notice the location of the active site in relation to the eight-stranded parallel β-barrel. Also pay attention to the location of the ligands in relation to the active site. The chloride ion is very close to the active site, indicating that this ligand is an allosteric activator.
Click here to highlight the amino acid residues bound to each ligand. The amino acid residues involved in calcium ion binding are Asn100, Arg 158, Asp 167, and His 201 and are highlighted gold. The amino acid residues involved in chloride ion binding are Arg 195, Asn 298, and Arg 337 and are highlighted blue. The water atoms in the molecule are also highlighted in tan. Note that the caclcium ion is bound to three water molecules and the chloride ion is bound to one water molecule. Pay attention to the proximity of the active site residues (light pink) to the ligand binding site residues.
Human salivary α-amylase contains a highly mobile glycine-rich loop that may act as a gateway for substrate binding. Click here to zoom in on the loop. The glycine residues are highlighted in bright blue. The glycine-rich loop may also be involved in a 'trap-release' mechanism in the hydrolysis of substrates.
Brayer GD, Yaoguang L, Withers SG. The structure of human pancreatic α-amylase at 1.8 A resolution and comparisons with related enzymes. Protein Science 1995; 4: 1730-1742. PubMed.
Buisson G, Duee E, Haser R, Payan F. Three dimensional structure of porcine pancreatic α-amylase at 2.9 A resolution. Role of calcium in structure and activity. The EMBO Journal. 1987; 6: 3909-3916. PubMed.
Ramasubbu N, Ragunath C, Mishra PJ, Thomas LM, Gyemant G, Kandra L. Human salivary α-amylase Trp58 situated at subsite -2 is critical for enzyme activity. Eur. J. Biochemistry 2004; 271: 2517-2529. PubMed.
Ramasubbu N, Paloth V, Luo Y, Brayer GD, Levine MJ. Structure of human salivary α-amylase at 1.6 A resolution: Implications for its role in the oral cavity. Acta Crystallagraphica 1996; D52: 435-446. PubMed.
Special thanks to:
Nathan Silva and David Marcey for their website An Introduction to Jmol Scripting
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