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1q4n

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Structural studies of Phe256Trp of human salivary alpha-amylase: implications for the role of a conserved water molecule and its associated chain in enzyme activity

Structural highlights

1q4n is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.07Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

AMY1A_HUMAN Calcium-binding enzyme that initiates starch digestion in the oral cavity (PubMed:12527308). Catalyzes the hydrolysis of internal (1->4)-alpha-D-glucosidic bonds, yielding a mixture of maltose, isomaltose, small amounts of glucose as well as small linear and branched oligosaccharides called dextrins (PubMed:12527308).^[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

In the mechanism of hydrolysis of starch by alpha-amylases, a conserved water molecule bridging two catalytic residues has been implicated. In human salivary alpha-amylase (HSAmy), this water (W641), observed in many alpha-amylase structures, is part of a chain of water molecules. To test the hypothesis that W641 may be involved in the mechanism, Phe256 in the close vicinity was mutated to a Trp residue. X-ray structure of F256W complexed to 2-amino-2-(hydroxyethyl)-1,3-propanediol at 2.1A revealed that the water chain is disrupted. In the F256W structure exhibits a positional shift in His305, characteristic of alpha-amylase complex structures. Kinetic analysis, in comparison with HSAmy, revealed that the mutant exhibited a 70-fold decrease in the specific activity for starch and significantly reduced k(cat) (20-fold) and K(m) (4-fold) for maltoheptaoside. Collectively, these results suggest that W641 and the chain of water molecules may be critical for the alpha-amylase activity.

Structural studies of a Phe256Trp mutant of human salivary alpha-amylase: implications for the role of a conserved water molecule in enzyme activity.,Ramasubbu N, Sundar K, Ragunath C, Rafi MM Arch Biochem Biophys. 2004 Jan 1;421(1):115-24. PMID:14678792^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ramasubbu N, Ragunath C, Mishra PJ. Probing the role of a mobile loop in substrate binding and enzyme activity of human salivary amylase. J Mol Biol. 2003 Jan 31;325(5):1061-76. PMID:12527308
↑ Ramasubbu N, Sundar K, Ragunath C, Rafi MM. Structural studies of a Phe256Trp mutant of human salivary alpha-amylase: implications for the role of a conserved water molecule in enzyme activity. Arch Biochem Biophys. 2004 Jan 1;421(1):115-24. PMID:14678792