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Architecture and functional dynamics of the pentafunctional AROM complex

DOI: 10.1038/s41589-020-0587-9 DOI Help

Authors: Harshul Arora Verasztó (University of Geneva; Max Planck Institute for Developmental Biology) , Maria Logotheti (Max Planck Institute for Developmental Biology) , Reinhard Albrecht (Max Planck Institute for Developmental Biology) , Alexander Leitner (ETH Zurich) , Hongbo Zhu (Max Planck Institute for Developmental Biology) , Marcus D. Hartmann (Max Planck Institute for Developmental Biology)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Chemical Biology , VOL 64

State: Published (Approved)
Published: July 2020
Diamond Proposal Number(s): 14307

Abstract: The AROM complex is a multifunctional metabolic machine with ten enzymatic domains catalyzing the five central steps of the shikimate pathway in fungi and protists. We determined its crystal structure and catalytic behavior, and elucidated its conformational space using a combination of experimental and computational approaches. We derived this space in an elementary approach, exploiting an abundance of conformational information from its monofunctional homologs in the Protein Data Bank. It demonstrates how AROM is optimized for spatial compactness while allowing for unrestricted conformational transitions and a decoupled functioning of its individual enzymatic entities. With this architecture, AROM poses a tractable test case for the effects of active site proximity on the efficiency of both natural metabolic systems and biotechnological pathway optimization approaches. We show that a mere colocalization of enzymes is not sufficient to yield a detectable improvement of metabolic throughput.

Journal Keywords: Enzymes; Metabolic pathways; Structural biology

Diamond Keywords: Enzymes

Subject Areas: Chemistry, Biology and Bio-materials


Instruments: B21-High Throughput SAXS

Other Facilities: P14 at PETRAIII

Added On: 23/07/2020 14:08

Discipline Tags:

Biochemistry Catalysis Chemistry Structural biology Organic Chemistry Life Sciences & Biotech

Technical Tags:

Scattering Small Angle X-ray Scattering (SAXS)