6M4Y

Structure of a R371A mutant of a Group II PLP dependent decarboxylase from Methanocaldococcus jannaschii

Summary for 6M4Y

• Entry DOI: 10.2210/pdb6m4y/pdb
• Related: 6JY1 6LDR 6LDS 6LDT
• Descriptor: L-tyrosine/L-aspartate decarboxylase, SULFATE ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: plp dependent decarboxylase, catalytic mutant, protein conformation, llp, internal aldimine, tyrosine, tyrosine decarboxylase, structure-activity relationship, lyase
• Biological source: Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)
• Total number of polymer chains: 1
• Total formula weight: 48141.15

Authors

Manoj, N.,Chellam Gayathri, S. (deposition date: 2020-03-09, release date: 2020-12-02, Last modification date: 2023-11-29)

Primary citation

Gayathri, S.C.,Manoj, N.
Crystallographic Snapshots of the Dunathan and Quinonoid Intermediates provide Insights into the Reaction Mechanism of Group II Decarboxylases.
J.Mol.Biol., 432:166692-166692, 2020

PubMed Abstract: PLP-dependent enzymes catalyze a plethora of chemical reactions affecting diverse physiological functions. Here we report the structural determinants of the reaction mechanism in a Group II PLP-dependent decarboxylase by assigning two early intermediates. The in-crystallo complexes of the PLP bound form, and the Dunathan and quinonoid intermediates, allowed direct observation of the active site interactions. The structures reveal that a subtle rearrangement of a conserved Arg residue in concert with a water-mediated interaction with the carboxylate of the Dunathan intermediate, appears to directly stabilize the alignment and facilitate the release of CO to yield the quinonoid. Modeling indicates that the conformational change of a dynamic catalytic loop to a closed form controls a conserved network of hydrogen bond interactions between catalytic residues to protonate the quinonoid. Our results provide a structural framework to elucidate mechanistic roles of residues that govern reaction specificity and catalysis in PLP-dependent decarboxylation.

PubMed: 33122004
DOI: 10.1016/j.jmb.2020.10.026

Experimental method

X-RAY DIFFRACTION (2.1 Å)