Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form
As of April 1st VIVO Scientific Profiles will no longer updated for faculty, and the link to VIVO will be removed from the library website. Faculty profile pages will continue to be updated via Interfolio. VIVO will continue being used behind the scenes to update graduate student profiles. Please contact helplib@scripps.edu if you have questions.
How to download citations from VIVO | Alternative profile options

Observation of covalent intermediates in an enzyme mechanism at atomic resolution

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

related to degree

  • Mitchell, Michael, Ph.D. in Chemistry, Scripps Research 1997 - 2002

authors

  • Heine, A.
  • DeSantis, G.
  • Luz, J. G.
  • Mitchell, Michael
  • Wong, Chi-Huey
  • Wilson, Ian

publication date

  • October 2001

journal

  • Science  Journal

abstract

  • In classical enzymology, intermediates and transition states in a catalytic mechanism are usually inferred from a series of biochemical experiments. Here, we derive an enzyme mechanism from true atomic-resolution x-ray structures of reaction intermediates. Two ultra-high resolution structures of wild-type and mutant d-2-deoxyribose-5-phosphate (DRP) aldolase complexes with DRP at 1.05 and 1.10 angstroms unambiguously identify the postulated covalent carbinolamine and Schiff base intermediates in the aldolase mechanism. In combination with site-directed mutagenesis and (1)H nuclear magnetic resonance, we can now propose how the heretofore elusive C-2 proton abstraction step and the overall stereochemical course are accomplished. A proton relay system appears to activate a conserved active-site water that functions as the critical mediator for proton transfer.

subject areas

  • Aldehyde-Lyases
  • Amino Acid Substitution
  • Binding Sites
  • Catalysis
  • Chemistry, Physical
  • Crystallization
  • Crystallography, X-Ray
  • Escherichia coli
  • Hydrogen Bonding
  • Hydrogen-Ion Concentration
  • Ligands
  • Lysine
  • Models, Chemical
  • Mutagenesis, Site-Directed
  • Mutation
  • Nuclear Magnetic Resonance, Biomolecular
  • Physicochemical Phenomena
  • Protein Conformation
  • Protein Folding
  • Protein Structure, Tertiary
  • Protons
  • Ribosemonophosphates
  • Schiff Bases
  • Water
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.1063601

PubMed ID

  • 11598300
scroll to property group menus

Additional Document Info

start page

  • 369

end page

  • 374

volume

  • 294

issue

  • 5541

©2022 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support