The Interaction of Isopenicillin N Synthase with Homologated Substrate Analogues δ-(L-α-Aminoadipoyl)-L-homocysteinyl-D-Xaa Characterised by Protein Crystallography

ChemBioChem ◽  
2013 ◽  
Vol 14 (5) ◽  
pp. 599-606 ◽  
Author(s):  
Adam Daruzzaman ◽  
Ian J. Clifton ◽  
Robert M. Adlington ◽  
Jack E. Baldwin ◽  
Peter J. Rutledge
Keyword(s):  
Protein Crystallography ◽  
Substrate Analogues ◽  
Isopenicillin N

Structural Studies on the Reaction of Isopenicillin N Synthase with the Truncated Substrate Analogues δ-(l-α-aminoadipoyl)-l-cysteinyl-glycine and δ-(l-α-aminoadipoyl)-l-cysteinyl-d-alanine†,‡

Biochemistry ◽  
2005 ◽  
Vol 44 (17) ◽  
pp. 6619-6628 ◽  
Author(s):  
Alexandra J. Long ◽  
Ian J. Clifton ◽  
Peter L. Roach ◽  
Jack E. Baldwin ◽  
Peter J. Rutledge ◽  
...  
Keyword(s):  
Structural Studies ◽  
Substrate Analogues ◽  
Isopenicillin N

Interactions of Isopenicillin N Synthase with Cyclopropyl-Containing Substrate Analogues Reveal New Mechanistic Insight†,‡

Biochemistry ◽  
2007 ◽  
Vol 46 (16) ◽  
pp. 4755-4762 ◽  
Author(s):  
Annaleise R. Howard-Jones ◽  
Jonathan M. Elkins ◽  
Ian J. Clifton ◽  
Peter L. Roach ◽  
Robert M. Adlington ◽  
...  
Keyword(s):  
Substrate Analogues ◽  
Mechanistic Insight ◽  
Isopenicillin N

Protein crystallography facility for the International Space Station

1995 ◽  
Author(s):  
William McDonald ◽  
Craig Smith ◽  
John Nordness ◽  
James Fountain ◽  
Lawrence DeLucas
Keyword(s):  
International Space Station ◽  
Protein Crystallography ◽  
Space Station ◽  
International Space

Protein Crystallography in Drug Discovery

2008 ◽  
Vol 9 (12) ◽  
pp. 1048-1053 ◽  
Author(s):  
Fernanda Canduri ◽  
Walter de Azevedo Jr.
Keyword(s):  
Drug Discovery ◽  
Protein Crystallography

scholarly journals Probing the ionization state of substrate α-d-glucopyranosyl phosphate bound to glycogen phosphorylase b

1995 ◽  
Vol 308 (3) ◽  
pp. 1017-1023 ◽  
Author(s):  
I P Street ◽  
S G Withers
Keyword(s):  
Active Site ◽  
Glycogen Phosphorylase ◽  
Ph Dependence ◽  
Substrate Inhibition ◽  
19F Nmr ◽  
Ionization State ◽  
Nmr Studies ◽  
Substrate Analogues ◽  
Glycogen Phosphorylase B ◽  
Pka Value

The ionization state of the substrate alpha-D-glucopyranosyl phosphate bound at the active site of glycogen phosphorylase has been probed by a number of techniques. Values of Ki determined for a series of substrate analogue inhibitors in which the phosphate moiety bears differing charges suggest that the enzyme will bind both the monoanionic and dianionic substrates with approximately equal affinity. These results are strongly supported by 31P- and 19F-NMR studies of the bound substrate analogues alpha-D-glucopyranosyl 1-methylenephosphonate and 2-deoxy-2-fluoro-alpha-D-glucopyranosyl phosphate, which also suggest that the substrate can be bound in either ionization state. The pH-dependences of the inhibition constants K1 for these two analogues, which have substantially different phosphate pK2 values (7.3 and 5.9 respectively), are found to be essentially identical with the pH-dependence of K(m) values for the substrate, inhibition decreasing according to an apparent pKa value of 7.2. This again indicates that there is no specificity for monoanion or dianion binding and also reveals that binding is associated with the uptake of a proton. As the bound substrate is not protonated, this proton must be taken up by the proton.

scholarly journals Studies on the Interaction of Aldolase with Substrate Analogues

1969 ◽  
Vol 244 (1) ◽  
pp. 126-134
Author(s):  
I A Rose ◽  
E L O'Connell
Keyword(s):  
Substrate Analogues

scholarly journals Activation modes in biocatalytic radical cyclization reactions

2021 ◽  
Author(s):  
Yuxuan Ye ◽  
Haigen Fu ◽  
Todd K Hyster
Keyword(s):  
Heme Iron ◽  
Radical Cyclization ◽  
Cytochrome P450 Monooxygenases ◽  
Radical Cyclizations ◽  
Cyclization Reactions ◽  
Complex Molecules ◽  
P450 Monooxygenases ◽  
Non Heme Iron ◽  
Essential Reactions ◽  
Isopenicillin N

Abstract Radical cyclizations are essential reactions in the biosynthesis of secondary metabolites and the chemical synthesis of societally valuable molecules. In this review, we highlight the general mechanisms utilized in biocatalytic radical cyclizations. We specifically highlight cytochrome P450 monooxygenases (P450s) involved in the biosynthesis of mycocyclosin and vancomycin, non-heme iron- and α-ketoglutarate-dependent dioxygenases (Fe/αKGDs) used in the biosynthesis of kainic acid, scopolamine, and isopenicillin N, and radical S-adenosylmethionine (SAM) enzymes that facilitate the biosynthesis of oxetanocin A, menaquinone, and F420. Beyond natural mechanisms, we also examine repurposed flavin-dependent ‘ene’-reductases (ERED) for non-natural radical cyclization. Overall, these general mechanisms underscore the opportunity for enzymes to augment and enhance the synthesis of complex molecules using radical mechanisms.

Beyond substrate analogues: new inhibitor chemotypes for glycosyltransferases

MedChemComm ◽  
2014 ◽  
Vol 5 (8) ◽  
pp. 1106-1125 ◽  
Author(s):  
Lauren Tedaldi ◽  
Gerd K. Wagner
Keyword(s):  
Acceptor Substrate ◽  
Substrate Analogues

New inhibitor chemotypes for glycosyltransferases, which are not structurally derived from either donor or acceptor substrate, are being reviewed.

Sign in / Sign up

Export Citation Format

Share Document