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@ARTICLE{Bokhove:95792,
author = {Bokhove, M. and Yoshida, H. and Hensgens, C. M. H. and van
der Laan, J. M. and Sutherland, J. D. and Dijkstra, B. W.
and DESY},
title = {{S}tructures of an isopenicillin {N} converting
{N}tn-hydrolase reveal different catalytic roles for the
active site residues of precursor and mature enzyme.},
journal = {Structure},
volume = {18},
issn = {0969-2126},
address = {London [u.a.]},
publisher = {Elsevier Science},
reportid = {PHPPUBDB-19255},
pages = {301-308},
year = {2010},
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.},
keywords = {Acyltransferases: chemistry / Acyltransferases: metabolism
/ Amidohydrolases: chemistry / Amidohydrolases: metabolism /
Catalysis / Catalytic Domain / Crystallography, X-Ray /
Cysteine: chemistry / Cysteine: metabolism / Hydrolysis /
Models, Molecular / Penicillin-Binding Proteins: chemistry /
Penicillin-Binding Proteins: metabolism / Penicillins:
chemistry / Penicillins: metabolism / Protein Conformation /
Penicillin-Binding Proteins (NLM Chemicals) / Penicillins
(NLM Chemicals) / Cysteine (NLM Chemicals) /
Acyltransferases (NLM Chemicals) /
acyl-CoA-6-aminopenicillanic acid acyltransferase (NLM
Chemicals) / Amidohydrolases (NLM Chemicals) / N-terminal
nucleophile hydrolase (NLM Chemicals) / penicillin N (NLM
Chemicals)},
cin = {EMBL},
ddc = {570},
cid = {$I:(DE-H253)EMBL_-2012_-20130307$},
pnm = {DORIS Beamline BW7 (POF2-54G13)},
pid = {G:(DE-H253)POF2-BW7-20130405},
experiment = {EXP:(DE-H253)D-BW7-20150101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:20223213},
UT = {WOS:000275492000007},
doi = {10.1016/j.str.2010.01.005},
url = {https://bib-pubdb1.desy.de/record/95792},
}