2X1C

The crystal structure of precursor acyl coenzyme A:isopenicillin N acyltransferase from Penicillium chrysogenum

Summary for 2X1C

• Entry DOI: 10.2210/pdb2x1c/pdb
• Related: 2X1D 2X1E
• Descriptor: ACYL-COENZYME, SULFATE ION, GLYCEROL, ... (5 entities in total)
• Functional Keywords: zymogen, transferase, ntn-hydrolase, penicillin biosynthesis, acyltransferase, antibiotic biosynthesis
• Biological source: PENICILLIUM CHRYSOGENUM
• Total number of polymer chains: 4
• Total formula weight: 161132.60

Authors

Bokhove, M.,Yoshida, H.,Hensgens, C.M.H.,van der Laan, J.M.,Sutherland, J.D.,Dijkstra, B.W. (deposition date: 2009-12-23, release date: 2010-03-09, Last modification date: 2024-05-08)

Primary citation

Bokhove, M.,Yoshida, H.,Hensgens, C.M.H.,Van Der Laan, J.M.,Sutherland, J.D.,Dijkstra, B.W.
Structures of an Isopenicillin N Converting Ntn-Hydrolase Reveal Different Catalytic Roles for the Active Site Residues of Precursor and Mature Enzyme.
Structure, 18:301-, 2010

PubMed Abstract: Penicillium chrysogenum Acyl coenzyme A:isopenicillin N acyltransferase (AT) performs the last step in the biosynthesis of hydrophobic penicillins, exchanging the hydrophilic side chain of a precursor for various hydrophobic side chains. Like other N-terminal nucleophile hydrolases AT is produced as an inactive precursor that matures upon posttranslational cleavage. The structure of a Cys103Ala precursor mutant shows that maturation is autoproteolytic, initiated by Cys103 cleaving its preceding peptide bond. The crystal structure of the mature enzyme shows that after autoproteolysis residues 92-102 fold outwards, exposing a buried pocket. This pocket is structurally and chemically flexible and can accommodate substrates of different size and polarity. Modeling of a substrate-bound state indicates the residues important for catalysis. Comparison of the proposed autoproteolytic and substrate hydrolysis mechanisms shows that in both events the same catalytic residues are used, but that they perform different roles in catalysis.

PubMed: 20223213
DOI: 10.1016/J.STR.2010.01.005

Experimental method

X-RAY DIFFRACTION (1.85 Å)