1P1X

Comparison of class I aldolase binding site architecture based on the crystal structure of 2-deoxyribose-5-phosphate aldolase determined at 0.99 Angstrom resolution

Summary for 1P1X

• Entry DOI: 10.2210/pdb1p1x/pdb
• Related: 1JCJ 1JCL
• Descriptor: Deoxyribose-phosphate aldolase (2 entities in total)
• Functional Keywords: alpha-beta barrel, tim barrel, lyase
• Biological source: Escherichia coli K-12
• Cellular location: Cytoplasm: P0A6L0
• Total number of polymer chains: 2
• Total formula weight: 55813.93

Authors

Heine, A.,Luz, J.G.,Wong, C.H.,Wilson, I.A. (deposition date: 2003-04-14, release date: 2004-06-01, Last modification date: 2024-02-14)

Primary citation

Heine, A.,Luz, J.G.,Wong, C.H.,Wilson, I.A.
Analysis of the class I aldolase binding site architecture based on the crystal structure of 2-deoxyribose-5-phosphate aldolase at 0.99A resolution.
J.Mol.Biol., 343:1019-1034, 2004

PubMed Abstract: The crystal structure of the bacterial (Escherichia coli) class I 2-deoxyribose-5-phosphate aldolase (DERA) has been determined by Se-Met multiple anomalous dispersion (MAD) methods at 0.99A resolution. This structure represents the highest-resolution X-ray structure of an aldolase determined to date and enables a true atomic view of the enzyme. The crystal structure shows the ubiquitous TIM alpha/beta barrel fold. The enzyme contains two lysine residues in the active site. Lys167 forms the Schiff base intermediate, whereas Lys201, which is in close vicinity to the reactive lysine residue, is responsible for the perturbed pK(a) of Lys167 and, hence, also a key residue in the reaction mechanism. DERA is the only known aldolase that is able to use aldehydes as both aldol donor and acceptor molecules in the aldol reaction and is, therefore, of particular interest as a biocatalyst in synthetic organic chemistry. The uncomplexed DERA structure enables a detailed comparison with the substrate complexes and highlights a conformational change in the phosphate-binding site. Knowledge of the enzyme active-site environment has been the basis for exploration of catalysis of non-natural substrates and of mutagenesis of the phosphate-binding site to expand substrate specificity. Detailed comparison with other class I aldolase enzymes and DERA enzymes from different organisms reveals a similar geometric arrangement of key residues and implies a potential role for water as a general base in the catalytic mechanism.

PubMed: 15476818
DOI: 10.1016/j.jmb.2004.08.066

Experimental method

X-RAY DIFFRACTION (0.99 Å)