Comprehensive Structural Characterization of the Bacterial Homospermidine Synthase-an Essential Enzyme of the Polyamine Metabolism

Scientific Reports
Sebastian KrossaAxel J Scheidig

Abstract

The highly conserved bacterial homospermidine synthase (HSS) is a key enzyme of the polyamine metabolism of many proteobacteria including pathogenic strains such as Legionella pneumophila and Pseudomonas aeruginosa; The unique usage of NAD(H) as a prosthetic group is a common feature of bacterial HSS, eukaryotic HSS and deoxyhypusine synthase (DHS). The structure of the bacterial enzyme does not possess a lysine residue in the active center and thus does not form an enzyme-substrate Schiff base intermediate as observed for the DHS. In contrast to the DHS the active site is not formed by the interface of two subunits but resides within one subunit of the bacterial HSS. Crystal structures of Blastochloris viridis HSS (BvHSS) reveal two distinct substrate binding sites, one of which is highly specific for putrescine. BvHSS features a side pocket in the direct vicinity of the active site formed by conserved amino acids and a potential substrate discrimination, guiding, and sensing mechanism. The proposed reaction steps for the catalysis of BvHSS emphasize cation-π interaction through a conserved Trp residue as a key stabilizer of high energetic transition states.

References

Apr 7, 1988·Nature·P Carter, J A Wells
Jun 20, 1997·The Journal of Biological Chemistry·E C WolffM H Park
Sep 20, 1997·Science·K U WendtG E Schulz
Oct 15, 1998·Proceedings of the National Academy of Sciences of the United States of America·W ZhongD A Dougherty
Dec 28, 1999·Proceedings of the National Academy of Sciences of the United States of America·D Ober, T Hartmann
Aug 23, 2001·Proceedings of the National Academy of Sciences of the United States of America·N A BakerJ A McCammon
Aug 5, 1997·Chemical Reviews·Jennifer C. Ma, Dennis A. Dougherty
Jul 2, 2003·Acta Crystallographica. Section D, Biological Crystallography·Elizabeth PottertonEleanor Dodson
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Gerard J KleywegtT Alwyn Jones
Jan 24, 2006·Journal of Biochemistry·Yoshihiko IkeguchiAnthony E Pegg
Apr 15, 2008·Molecular Microbiology·Pratik Shah, Edwin Swiatlo
Feb 17, 2009·Structure·Wijnand T M MooijAnastassis Perrakis
Feb 24, 2009·Annual Review of Biochemistry·Hiroshi Nikaido
Feb 28, 2009·Nature Protocols·Lawrence A Kelley, Michael J E Sternberg
Apr 29, 2009·Biochemistry·Marina KonortyAbraham Minsky
May 9, 2009·Nature·Preeti SainiThomas E Dever
Jul 16, 2009·IUBMB Life·Anthony E Pegg
Nov 6, 2009·The Journal of Physical Chemistry. a·Michael S MarshallC David Sherrill
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Nov 6, 2010·Journal of Computer-aided Molecular Design·Markus A Lill, Matthew L Danielson
Feb 15, 2011·Methods in Molecular Biology·Anthony E Pegg, Robert A Casero
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Philip R Evans
Jul 12, 2011·Journal of Bacteriology·Gheyath K NasrallahRafael A Garduño
Aug 6, 2011·Journal of the American Chemical Society·Juan A FaraldosRudolf K Allemann

❮ Previous
Next ❯

Citations

Mar 12, 2016·Journal of Medicinal Chemistry·Bo WangPatrick M Woster
Jul 30, 2016·The Biochemical Journal·Anthony J Michael
Jun 29, 2017·The Biochemical Journal·Anthony J Michael
Mar 15, 2020·Biotechnology Journal·Melanie MindtVolker F Wendisch

❮ Previous
Next ❯

Datasets Mentioned

BETA
C-3′

Methods Mentioned

BETA
deamination
PCR
size-exclusion chromatography

Software Mentioned

HOLLOW
PyMOL
ChemStation
APBS
ARP
Pointless
PDB2PQR
wARP
PROPKA
Coot

Related Concepts

Related Feeds

Bacterial Protein Structures

Bacterial protein structures can expedite the development of novel antibiotics. Here is the latest research on bacterial proteins and the resolution of their structures.

Bacterial Protein Structures (ASM)

Bacterial protein structures can expedite the development of novel antibiotics. Here is the latest research on bacterial proteins and the resolution of their structures.