4YR1

Crystal Structure of E. Coli Alkaline Phosphatase D101A/D153A in complex with inorganic phosphate

Summary for 4YR1

• Entry DOI: 10.2210/pdb4yr1/pdb
• Descriptor: Alkaline phosphatase, ZINC ION, PHOSPHATE ION, ... (5 entities in total)
• Functional Keywords: hydrolase
• Biological source: Escherichia coli (strain K12)
• Total number of polymer chains: 2
• Total formula weight: 93354.94

Authors

Peck, A.,Herschlag, D. (deposition date: 2015-03-13, release date: 2015-04-29, Last modification date: 2019-12-25)

Primary citation

Sunden, F.,Peck, A.,Salzman, J.,Ressl, S.,Herschlag, D.
Extensive site-directed mutagenesis reveals interconnected functional units in the Alkaline Phosphatase active site.
Elife, 4:-, 2015

PubMed Abstract: Enzymes enable life by accelerating reaction rates to biological timescales. Conventional studies have focused on identifying the residues that have a direct involvement in an enzymatic reaction, but these so-called 'catalytic residues' are embedded in extensive interaction networks. Although fundamental to our understanding of enzyme function, evolution, and engineering, the properties of these networks have yet to be quantitatively and systematically explored. We dissected an interaction network of five residues in the active site of Escherichia coli alkaline phosphatase. Analysis of the complex catalytic interdependence of specific residues identified three energetically independent but structurally interconnected functional units with distinct modes of cooperativity. From an evolutionary perspective, this network is orders of magnitude more probable to arise than a fully cooperative network. From a functional perspective, new catalytic insights emerge. Further, such comprehensive energetic characterization will be necessary to benchmark the algorithms required to rationally engineer highly efficient enzymes.

PubMed: 25902402
DOI: 10.7554/eLife.06181

Experimental method

X-RAY DIFFRACTION (2.24 Å)