8A28

Structure of the astacin zymogen of LAST-MAM from Limulus polyphemus

Summary for 8A28

• Entry DOI: 10.2210/pdb8a28/pdb
• Descriptor: Metalloendopeptidase, ZINC ION, MAGNESIUM ION, ... (7 entities in total)
• Functional Keywords: metallopeptidase zymogen, hydrolase
• Biological source: Limulus polyphemus (Atlantic horseshoe crab)
• Total number of polymer chains: 2
• Total formula weight: 87619.26

Authors

Guevara, T.,Rodriguez Banqueri, A. (deposition date: 2022-06-02, release date: 2022-10-19, Last modification date: 2024-11-06)

Primary citation

Guevara, T.,Rodriguez-Banqueri, A.,Stocker, W.,Becker-Pauly, C.,Gomis-Ruth, F.X.
Zymogenic latency in an ∼250-million-year-old astacin metallopeptidase.
Acta Crystallogr D Struct Biol, 78:1347-1357, 2022

PubMed Abstract: The horseshoe crab Limulus polyphemus is one of few extant Limulus species, which date back to ∼250 million years ago under the conservation of a common Bauplan documented by fossil records. It possesses the only proteolytic blood-coagulation and innate immunity system outside vertebrates and is a model organism for the study of the evolution and function of peptidases. The astacins are a family of metallopeptidases that share a central ∼200-residue catalytic domain (CD), which is found in >1000 species across holozoans and, sporadically, bacteria. Here, the zymogen of an astacin from L. polyphemus was crystallized and its structure was solved. A 34-residue, mostly unstructured pro-peptide (PP) traverses, and thus blocks, the active-site cleft of the CD in the opposite direction to a substrate. A central `PP motif' (F-E-G-D-I) adopts a loop structure which positions Asp38 to bind the catalytic metal, replacing the solvent molecule required for catalysis in the mature enzyme according to an `aspartate-switch' mechanism. Maturation cleavage of the PP liberates the cleft and causes the rearrangement of an `activation segment'. Moreover, the mature N-terminus is repositioned to penetrate the CD moiety and is anchored to a buried `family-specific' glutamate. Overall, this mechanism of latency is reminiscent of that of the other three astacins with known zymogenic and mature structures, namely crayfish astacin, human meprin β and bacterial myroilysin, but each shows specific structural characteristics. Remarkably, myroilysin lacks the PP motif and employs a cysteine instead of the aspartate to block the catalytic metal.

PubMed: 36322418
DOI: 10.1107/S2059798322009688

Experimental method

X-RAY DIFFRACTION (2.4 Å)