TY  - JOUR
AU  - Bokhove, M.
AU  - Yoshida, H.
AU  - Hensgens, C. M. H.
AU  - van der Laan, J. M.
AU  - Sutherland, J. D.
AU  - Dijkstra, B. W.
AU  - DESY
TI  - Structures of an isopenicillin N converting Ntn-hydrolase reveal different catalytic roles for the active site residues of precursor and mature enzyme.
JO  - Structure
VL  - 18
SN  - 0969-2126
CY  - London [u.a.]
PB  - Elsevier Science
M1  - PHPPUBDB-19255
SP  - 301-308
PY  - 2010
AB  - 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.
KW  - Acyltransferases: chemistry
KW  - Acyltransferases: metabolism
KW  - Amidohydrolases: chemistry
KW  - Amidohydrolases: metabolism
KW  - Catalysis
KW  - Catalytic Domain
KW  - Crystallography, X-Ray
KW  - Cysteine: chemistry
KW  - Cysteine: metabolism
KW  - Hydrolysis
KW  - Models, Molecular
KW  - Penicillin-Binding Proteins: chemistry
KW  - Penicillin-Binding Proteins: metabolism
KW  - Penicillins: chemistry
KW  - Penicillins: metabolism
KW  - Protein Conformation
KW  - Penicillin-Binding Proteins (NLM Chemicals)
KW  - Penicillins (NLM Chemicals)
KW  - Cysteine (NLM Chemicals)
KW  - Acyltransferases (NLM Chemicals)
KW  - acyl-CoA-6-aminopenicillanic acid acyltransferase (NLM Chemicals)
KW  - Amidohydrolases (NLM Chemicals)
KW  - N-terminal nucleophile hydrolase (NLM Chemicals)
KW  - penicillin N (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:20223213
UR  - <Go to ISI:>//WOS:000275492000007
DO  - DOI:10.1016/j.str.2010.01.005
UR  - https://bib-pubdb1.desy.de/record/95792
ER  -