Structural Basis for Glycyl Radical Formation By Pyruvate Formate-Lyase Activating Enzyme

Journal Article · Tue May 26 04:00:00 EDT 2009 · Proc. Nat. Acad. Sci. 105:16137,2008

OSTI ID:953597

Vey, J L; Yang, J; Li, M; Broderick, W E; Broderick, J B; Drennan, C L

Pyruvate formate-lyase activating enzyme generates a stable and catalytically essential glycyl radical on G{sup 734} of pyruvate formate-lyase via the direct, stereospecific abstraction of a hydrogen atom from pyruvate formate-lyase. The activase performs this remarkable feat by using an iron-sulfur cluster and S-adenosylmethionine (AdoMet), thus placing it among the AdoMet radical superfamily of enzymes. We report here structures of the substrate-free and substrate-bound forms of pyruvate formate-lyase-activating enzyme, the first structures of an AdoMet radical activase. To obtain the substrate-bound structure, we have used a peptide substrate, the 7-mer RVSGYAV, which contains the sequence surrounding G{sup 734}. Our structures provide fundamental insights into the interactions between the activase and the G{sup 734} loop of pyruvate formate-lyase and provide a structural basis for direct and stereospecific H atom abstraction from the buried G{sup 734}4 of pyruvate formate-lyase.

• Research Organization: Stanford Linear Accelerator Center (SLAC)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC02-76SF00515
• OSTI ID: 953597
• Report Number(s): SLAC-REPRINT-2009-286
• Journal Information: Proc. Nat. Acad. Sci. 105:16137,2008, Journal Name: Proc. Nat. Acad. Sci. 105:16137,2008 Journal Issue: 42 Vol. 105; ISSN 0027-8424; ISSN PNASA6
• Country of Publication: United States
• Language: English

Related Subjects

08 HYDROGEN
ATOMS
CRYSTALLOGRAPHY
ENZYMES
HYDROGEN
INTERACTIONS
METALLOPROTEINS
Other
OTHER
PEPTIDES
RADICALS