4re5 | pdb_00004re5

Acylaminoacyl peptidase complexed with a chloromethylketone inhibitor

spinqualitylabelsall models 4re5, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4re5 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACT, CL, MPD, Y3A Related: 4re6 Activity: Acylaminoacyl-peptidase, with EC number 3.4.19.1 Resources: FirstGlance, OCA, RCSB, PDBsum Function [APEH_AERPE] This enzyme catalyzes the hydrolysis of the N-terminal peptide bond of an N-acetylated peptide to generate an N-acetylated amino acid and a peptide with a free N-terminus. Publication Abstract from PubMed Acylaminoacyl peptidase (AAP) is an oligopeptidase that only cleaves short peptides or protein segments. In the case of AAP from Aeropyrum pernix (ApAAP), previous studies have led to a model in which the clamshell-like opening and closing of the enzyme provides the means of substrate-size selection. The closed form of the enzyme is catalytically active, while opening deactivates the catalytic triad. The crystallographic results presented here show that the open form of ApAAP is indeed functionally disabled. The obtained crystal structures also reveal that the closed form is penetrable to small ligands: inhibitor added to the pre-formed crystal was able to reach the active site of the rigidified protein, which is only possible through the narrow channel of the propeller domain. Molecular-dynamics simulations investigating the structure of the complexes formed with longer peptide substrates showed that their binding within the large crevice of the closed form of ApAAP leaves the enzyme structure unperturbed; however, their accessing the binding site seems more probable when assisted by opening of the enzyme. Thus, the open form of ApAAP corresponds to a scavenger of possible substrates, the actual cleavage of which only takes place if the enzyme is able to re-close. Catalytically distinct states captured in a crystal lattice: the substrate-bound and scavenger states of acylaminoacyl peptidase and their implications for functionality.,Menyhard DK, Orgovan Z, Szeltner Z, Szamosi I, Harmat V Acta Crystallogr D Biol Crystallogr. 2015 Mar 1;71(Pt 3):461-72. doi:, 10.1107/S1399004714026819. Epub 2015 Feb 26. PMID:25760596 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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