TY - JOUR
T1 - Recent advances in the structure and function of isopenicillin N synthase
AU - Kreisberg-Zakarin, Rachel
AU - Borovok, Ilya
AU - Yanko, Michaela
AU - Aharonowitz, Yair
AU - Cohen, Gerald
N1 - Funding Information:
We would like to thank Jim Remington, the University of Oregon, and Felix Frolow, Tel-Aviv University, for communicating preliminary results on the crystal structure of the Streptomyces jumonjinensis of IPNS, and the Israel Science Foundation for a grant, No. 488/97.
PY - 1999
Y1 - 1999
N2 - Isopenicillin N synthase is a key enzyme in the biosynthesis of penicillin and cephalosporin antibiotics, catalyzing the oxidative ring closure of δ-(L-α-aminoadipoyl)-L-cysteinyl-D-valine to form isopeniciliin N. Recent advances in our understanding of the unique chemistry of this enzyme have come through the combined application of spectroscopic, molecular genetic and crystallographic approaches and led to important new insights into the structure and function of this enzyme. Here we review new information on the nature of the endogenous ligands that constitute the ferrous iron active site, sequence evidence for a novel structural motif involved in iron binding in this and related non-heme iron dependent dioxygenases, crystal structure studies on the enzyme and its substrate complex and the impact of these and site-directed mutagenesis studies for unraveling the mechanism of the isopenicillin N synthase reaction.
AB - Isopenicillin N synthase is a key enzyme in the biosynthesis of penicillin and cephalosporin antibiotics, catalyzing the oxidative ring closure of δ-(L-α-aminoadipoyl)-L-cysteinyl-D-valine to form isopeniciliin N. Recent advances in our understanding of the unique chemistry of this enzyme have come through the combined application of spectroscopic, molecular genetic and crystallographic approaches and led to important new insights into the structure and function of this enzyme. Here we review new information on the nature of the endogenous ligands that constitute the ferrous iron active site, sequence evidence for a novel structural motif involved in iron binding in this and related non-heme iron dependent dioxygenases, crystal structure studies on the enzyme and its substrate complex and the impact of these and site-directed mutagenesis studies for unraveling the mechanism of the isopenicillin N synthase reaction.
KW - Active site
KW - Crystal structure
KW - Iron binding motif
KW - Isopenicillin N synthase
KW - Mechanism of action
UR - http://www.scopus.com/inward/record.url?scp=0033056377&partnerID=8YFLogxK
U2 - 10.1023/A:1001723202234
DO - 10.1023/A:1001723202234
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AN - SCOPUS:0033056377
SN - 0003-6072
VL - 75
SP - 33
EP - 39
JO - Antonie van Leeuwenhoek
JF - Antonie van Leeuwenhoek
IS - 1-2
ER -