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TitleStructural basis for the catalytic activity of filamentous human serine beta-lactamase-like protein LACTB.
Journal, issue, pagesStructure, Vol. 30, Issue 5, Page 685-696.e5, Year 2022
Publish dateMay 5, 2022
AuthorsMinghui Zhang / Laixing Zhang / Runyu Guo / Chun Xiao / Jian Yin / Sensen Zhang / Maojun Yang /
PubMed AbstractSerine beta-lactamase-like protein (LACTB) is a mammalian mitochondrial serine protease that can specifically hydrolyze peptide bonds adjacent to aspartic acid residues and is structurally related to ...Serine beta-lactamase-like protein (LACTB) is a mammalian mitochondrial serine protease that can specifically hydrolyze peptide bonds adjacent to aspartic acid residues and is structurally related to prokaryotic penicillin-binding proteins. Here, we determined the cryoelectron microscopy structures of human LACTB (hLACTB) filaments from wild-type protein, a middle region deletion mutant, and in complex with the inhibitor Z-AAD-CMK at 3.0-, 3.1-, and 2.8-Å resolution, respectively. Structural analysis and activity assays revealed that three interfaces are required for the assembly of hLACTB filaments and that the formation of higher order helical structures facilitates its cleavage activity. Further structural and enzymatic analyses of middle region deletion constructs indicated that, while this region is necessary for substrate hydrolysis, it is not required for filament formation. Moreover, the inhibitor-bound structure showed that hLACTB may cleave peptide bonds adjacent to aspartic acid residues. These findings provide the structural basis underlying hLACTB catalytic activity.
External linksStructure / PubMed:35247327
MethodsEM (single particle)
Resolution2.82 - 3.08 Å
Structure data

EMDB-31630, PDB-7v1y:
Serine beta-lactamase-like protein LACTB in complex with inhibitor
Method: EM (single particle) / Resolution: 2.82 Å

EMDB-31631, PDB-7v1z:
human Serine beta-lactamase-like protein LACTB
Method: EM (single particle) / Resolution: 2.98 Å

EMDB-31633, PDB-7v21:
human Serine beta-lactamase-like protein LACTB truncation variant
Method: EM (single particle) / Resolution: 3.08 Å

Source
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsHYDROLASE / mitochondrial intermembrane space protease / CYTOSOLIC PROTEIN

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