2QAP

Fructose-1,6-bisphosphate aldolase from Leishmania mexicana

Summary for 2QAP

• Entry DOI: 10.2210/pdb2qap/pdb
• Related: 1EPX 2QDG 2QDH
• Descriptor: Fructose-1,6-bisphosphate aldolase, PHOSPHATE ION (3 entities in total)
• Functional Keywords: beta barrel, aldolase, leishmania, fructose-1, 6-bisphosphate, c-teminal tail, lyase
• Biological source: Leishmania mexicana
• Total number of polymer chains: 4
• Total formula weight: 173276.93

Authors

Lafrance-Vanasse, J.,Sygusch, J. (deposition date: 2007-06-15, release date: 2007-08-21, Last modification date: 2023-08-30)

Primary citation

Lafrance-Vanasse, J.,Sygusch, J.
Carboxy-Terminus Recruitment Induced by Substrate Binding in Eukaryotic Fructose Bis-phosphate Aldolases
Biochemistry, 46:9533-9540, 2007

PubMed Abstract: The crystal structures of Leishmania mexicana fructose-1,6-bis(phosphate) aldolase in complex with substrate and competitive inhibitor, mannitol-1,6-bis(phosphate), were solved to 2.2 A resolution. Crystallographic analysis revealed a Schiff base intermediate trapped in the native structure complexed with substrate while the inhibitor was trapped in a conformation mimicking the carbinolamine intermediate. Binding modes corroborated previous structures reported for rabbit muscle aldolase. Amino acid substitution of Gly-312 to Ala, adjacent to the P1-phosphate binding site and unique to trypanosomatids, did not perturb ligand binding in the active site. Ligand attachment ordered amino acid residues 359-367 of the C-terminal region (353-373) that was disordered beyond Asp-358 in the unbound structure, revealing a novel recruitment mechanism of this region by aldolases. C-Terminal peptide ordering is triggered by P1-phosphate binding that induces conformational changes whereby C-terminal Leu-364 contacts P1-phosphate binding residue Arg-313. C-Terminal region capture synergizes additional interactions with subunit surface residues, not perturbed by P1-phosphate binding, and stabilizes C-terminal attachment. Amino acid residues that participate in the capturing interaction are conserved among class I aldolases, indicating a general recruitment mechanism whereby C-terminal capture facilitates active site interactions in subsequent catalytic steps. Recruitment accelerates the enzymatic reaction by using binding energy to reduce configurational entropy during catalysis thereby localizing the conserved C-terminus tyrosine, which mediates proton transfer, proximal to the active site enamine.

PubMed: 17661446
DOI: 10.1021/bi700615r

Experimental method

X-RAY DIFFRACTION (1.59 Å)