title: Insights into the mechanism of ligand binding to octopine dehydrogenase from Pecten maximus by NMR and crystallography.
abstract: Octopine dehydrogenase (OcDH) from the adductor muscle of the great scallop, Pecten maximus, catalyzes the NADH dependent, reductive condensation of L-arginine and pyruvate to octopine, NAD(+), and water during escape swimming and/or subsequent recovery. The structure of OcDH was recently solved and a reaction mechanism was proposed which implied an ordered binding of NADH, L-arginine and finally pyruvate. Here, the order of substrate binding as well as the underlying conformational changes were investigated by NMR confirming the model derived from the crystal structures. Furthermore, the crystal structure of the OcDH/NADH/agmatine complex was determined which suggests a key role of the side chain of L-arginine in protein cataylsis. Thus, the order of substrate binding to OcDH as well as the molecular signals involved in octopine formation can now be described in molecular detail.
authors.affiliation: Institute of Biochemistry, Heinrich-Heine-University, Duesseldorf, Germany. sander.smits@uni-duesseldorf.de
authors.forename: Sander H J
authors.initials: SH
authors.lastname: Smits
authors.forename: Tatu
authors.initials: T
authors.lastname: Meyer
authors.forename: Andre
authors.initials: A
authors.lastname: Mueller
authors.forename: Nadine
authors.initials: N
authors.lastname: van Os
authors.forename: Matthias
authors.initials: M
authors.lastname: Stoldt
authors.forename: Dieter
authors.initials: D
authors.lastname: Willbold
authors.forename: Lutz
authors.initials: L
authors.lastname: Schmitt
authors.forename: Manfred K
authors.initials: MK
authors.lastname: Grieshaber
mesh_terms: D000376:Agmatine / Q000494:pharmacology; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D018360:Crystallography, X-Ray; D008024:Ligands; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D049910:Pecten / Q000201:enzymology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D008024:Ligands; D000376:Agmatine; D000594:Amino Acid Oxidoreductases; C021903:D-octopine dehydrogenase
references.citation: Eur J Biochem. 1972 Sep 18;29(2):288-92
references.pmid: 4343089
references.citation: Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008 Sep 1;64(Pt 9):836-9
references.pmid: 18765918
references.citation: Acta Crystallogr D Biol Crystallogr. 1997 May 1;53(Pt 3):240-55
references.pmid: 15299926
references.citation: Eur J Biochem. 1975 Nov 1;59(1):185-91
references.pmid: 173532
references.citation: J Mol Biol. 2008 Aug 1;381(1):200-11
references.pmid: 18599075
references.citation: Nat Struct Biol. 1998 Jul;5(7):561-7
references.pmid: 9665169
references.citation: Bull Soc Chim Biol (Paris). 1959;41:735-42
references.pmid: 13837876
references.citation: FEBS J. 2007 Dec;274(24):6329-39
references.pmid: 18028427
references.citation: Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
references.pmid: 15572765
references.citation: Biochim Biophys Acta. 1969 Sep 30;191(1):46-57
references.pmid: 4310628
references.citation: Eur J Biochem. 1975 Nov 1;59(1):175-83
references.pmid: 1248
references.citation: Biochemistry. 1984 Mar 27;23(7):1348-53
references.pmid: 6722094
references.citation: Rev Physiol Biochem Pharmacol. 1994;125:43-147
references.pmid: 7984874
references.citation: Nat Struct Biol. 1998 Jul;5(7):593-601
references.pmid: 9665174
references.citation: Biochem Soc Trans. 1981 Aug;9(4):278-9
references.pmid: 7262443
references.citation: J Mol Biol. 2007 Oct 26;373(3):745-54
references.pmid: 17854830
references.citation: Nature. 1974 Jul 19;250(463):194-9
references.pmid: 4368490
references.citation: EMBO J. 1992 Sep;11(9):3289-95
references.pmid: 1380452
references.citation: Eur J Biochem. 1974 Jul 1;46(1):59-66
references.pmid: 4368817