7QP0

Crystal structure of metacaspase from candida glabrata with magnesium

Summary for 7QP0

• Entry DOI: 10.2210/pdb7qp0/pdb
• Descriptor: Metacaspase-1, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: metacaspase, protease, ca2+-dependent activation, apoptosis
• Biological source: [Candida] glabrata
• Total number of polymer chains: 2
• Total formula weight: 88311.83

Authors

Conchou, L.,Ballut, L.,Violot, S.,Aghajari, N. (deposition date: 2021-12-30, release date: 2023-01-11, Last modification date: 2024-01-31)

Primary citation

Conchou, L.,Doumeche, B.,Galisson, F.,Violot, S.,Dugelay, C.,Diesis, E.,Page, A.,Bienvenu, A.L.,Picot, S.,Aghajari, N.,Ballut, L.
Structural and molecular determinants of Candida glabrata metacaspase maturation and activation by calcium.
Commun Biol, 5:1158-1158, 2022

PubMed Abstract: Metacaspases are caspase-like homologs which undergo a complex maturation process involving multiple intra-chain cleavages resulting in a composite enzyme made of a p10 and a p20 domain. Their proteolytic activity involving a cysteine-histidine catalytic dyad, show peptide bond cleavage specificity in the C-terminal to lysine and arginine, with both maturation- and catalytic processes being calcium-dependent. Here, we present the structure of a metacaspase from the yeast Candida glabrata, CgMCA-I, in complex with a unique calcium along with a structure in which three magnesium ions are bound. We show that the Ca ion interacts with a loop in the vicinity of the catalytic site. The reorganization of this cation binding loop, by bringing together the two catalytic residues, could be one of the main structural determinants triggering metacaspase activation. Enzymatic exploration of CgMCA-I confirmed that the maturation process implies a trans mechanism with sequential cleavages.

PubMed: 36316540
DOI: 10.1038/s42003-022-04091-4

Experimental method

X-RAY DIFFRACTION (1.6 Å)