3UCC

Asymmetric complex of human neuron specific enolase-1-PGA/PEP

Summary for 3UCC

• Entry DOI: 10.2210/pdb3ucc/pdb
• Related: 1TE6 2AKM 2AKZ 3UCD
• Descriptor: Gamma-enolase, MAGNESIUM ION, 2-PHOSPHOGLYCERIC ACID, ... (5 entities in total)
• Functional Keywords: lyase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : P09104
• Total number of polymer chains: 2
• Total formula weight: 96625.66

Authors

Qin, J.,Chai, G.,Brewer, J.,Lovelace, L.,Lebioda, L. (deposition date: 2011-10-26, release date: 2012-08-22, Last modification date: 2023-09-13)

Primary citation

Qin, J.,Chai, G.,Brewer, J.M.,Lovelace, L.L.,Lebioda, L.
Structures of asymmetric complexes of human neuron specific enolase with resolved substrate and product and an analogous complex with two inhibitors indicate subunit interaction and inhibitor cooperativity.
J.Inorg.Biochem., 111:187-194, 2012

PubMed Abstract: In the presence of magnesium, enolase catalyzes the dehydration of 2-phospho-d-glycerate (PGA) to phosphoenolpyruvate (PEP) in glycolysis and the reverse reaction in gluconeogensis at comparable rates. The structure of human neuron specific enolase (hNSE) crystals soaked in PGA showed that the enzyme is active in the crystals and produced PEP; conversely soaking in PEP produced PGA. Moreover, the hNSE dimer contains PGA bound in one subunit and PEP or a mixture of PEP and PGA in the other. Crystals soaked in a mixture of competitive inhibitors tartronate semialdehyde phosphate (TSP) and lactic acid phosphate (LAP) showed asymmetry with TSP binding in the same site as PGA and LAP in the PEP site. Kinetic studies showed that the inhibition of NSE by mixtures of TSP and LAP is stronger than predicted for independently acting inhibitors. This indicates that in some cases inhibition of homodimeric enzymes by mixtures of inhibitors ("heteroinhibition") may offer advantages over single inhibitors.

PubMed: 22437160
DOI: 10.1016/j.jinorgbio.2012.02.011

Experimental method

X-RAY DIFFRACTION (1.5 Å)