6ifg

Crystal structure of M1 zinc metallopeptidase E323A mutant bound to Tyr-ser-ala substrate from Deinococcus radiodurans

spinqualitylabelsall models 6ifg, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ifg is a 4 chain structure with sequence from Deinococcus and Deinococcus radiodurans R1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Ligands: FMT, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q9RVZ5_DEIRA Publication Abstract from PubMed Zinc metallopeptidases of the M1 family (M1 peptidases) with unique metal binding motif HEXXH(X)18E regulate many important biological processes such as tumor growth, angiogenesis, hormone regulation, and immune cell development. Typically, these enzymes exist in three-domain [N-terminal domain (N-domain), catalytic domain, and C-terminal domain (C-domain)] or four-domain (N-domain, catalytic domain, middle domain, and C-domain) format in which N-domain and catalytic domain are more conserved. The C-domain plays important roles in substrate binding and gating. In this study we report the first structure of a two-domain (N-domain and catalytic domain) M1 peptidase at 2.05A resolution. Despite the lack of C-domain, the enzyme is active and prefers peptide substrates with large hydrophobic N-terminal residues. Its substrate-bound structure was determined at 1.9A resolution. Structural analyses supported by site directed mutagenesis and molecular dynamics simulations reveal structural features that could compensate for the lack of C-domain. A unique loop insertion (loop A) in the N-domain has important roles in gating and desolvation of active site. Three Arg residues of the catalytic domain are involved in substrate-binding roles typically played by positively charged residues of C-domain in other M1 peptidases. Further, its unique exopeptidase sequence motif, LALET, creates a more hydrophobic environment at the S1 subsite (which binds N-terminal residue of the substrate in aminopeptidases) than the more common GXMEN motif in the family. This leads to high affinity for large hydrophobic residues in the S1 subsite, which contributes towards efficient substrate binding in absence of C-domain. Two-domain aminopeptidase of M1 family: Structural features for substrate binding and gating in absence of C-terminal domain.,Agrawal R, Goyal VD, Kumar A, Gaur NK, Jamdar SN, Kumar A, Makde RD J Struct Biol. 2019 Oct 1;208(1):51-60. doi: 10.1016/j.jsb.2019.07.010. Epub 2019, Jul 25. PMID:31351924 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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