6KP1

Crystal structure of two domain M1 zinc metallopeptidase E323A mutant bound to L-methionine amino acid

Summary for 6KP1

• Entry DOI: 10.2210/pdb6kp1/pdb
• Descriptor: Zinc metalloprotease, putative, ZINC ION, SODIUM ION, ... (5 entities in total)
• Functional Keywords: metalloprotease, hydrolase
• Biological source: Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / LMG 4051 / NBRC 15346 / NCIMB 9279 / R1 / VKM B-1422)
• Total number of polymer chains: 2
• Total formula weight: 103570.81

Authors

Agrawal, R.,Kumar, A.,Kumar, A.,Makde, R.D. (deposition date: 2019-08-13, release date: 2020-06-24, Last modification date: 2023-11-22)

Primary citation

Agrawal, R.,Goyal, V.D.,Singh, R.,Kumar, A.,Jamdar, S.N.,Kumar, A.,Makde, R.D.
Structural basis for the unusual substrate specificity of unique two-domain M1 metallopeptidase.
Int.J.Biol.Macromol., 147:304-313, 2020

PubMed Abstract: M1 metallopeptidases regulate many important biological processes such as angiogenesis, tumour growth, hormone regulation, and immune cell development. Knowledge of substrate specificity mechanism in this family is valuable. An M1 peptidase from Deinococcus radiodurans (M1dr) with preference for bulky hydrophobic residues at N-terminus of peptide substrates was recently reported. In contrast to Escherichia coli aminopeptidase N, a previously characterized M1 peptidase, M1dr exhibits reduced activity towards peptides with N-terminal Arg or Ala residue. In order to illuminate structural basis of substrate specificity, we report several crystal structures of M1dr with different amino acids bound to the active site. Structural analysis indicated that the enzyme makes subtle adjustments to multiple residues leading to significant volume change of the active site cavity to accommodate residues of varying sizes (Leu to Trp). This study further reveals that the low preference for Arg at N-terminus of peptide substrate arises from a non-productive conformation in which many of the Arg molecules bind where they block the proton donor essential for the peptidase reaction. Hence, this study illuminates the substrate-binding mechanism and also reveals the structural basis for the substrate specificity of M1dr enzyme.

PubMed: 31923495
DOI: 10.1016/j.ijbiomac.2019.12.239

Experimental method

X-RAY DIFFRACTION (2.19 Å)