Evidence map›Paper›PMID 21675920›Full record

ReviewAnnual review of biochemistry2011

Enzymatic transition states, transition-state analogs, dynamics, thermodynamics, and lifetimes.

Vern L Schramm

Abstract readReview
In one paragraph

Review in Annual review of biochemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

99 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Review
  8. Transition State Analysis of SAMHD1 from PrimaryJournal of the American Chemical Society · 2025
    Article
  9. Chemical Tools for Probing the Ub/Ubl Conjugation Cascades.Chembiochem : a European journal of chemical biology · 2025
    Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. Kinetics and Mechanism of Azole n-π*-Catalyzed Amine Acylation.Journal of the American Chemical Society · 2023
    Article
  15. Article
  16. Article
  17. Capturing the free energy of transition state stabilization: insights from the inhibition of mandelate racemase.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
    Review
  18. Article
  19. Protein dynamics: The future is bright and complicated!Structural dynamics (Melville, N.Y.) · 2023
    Article
  20. Article

39 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

1 author.

Vern L SchrammDepartment of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA. vern.schramm@einstein.yu.edu

Funding

Proton Transfer Dynamics in Heme-Copper OxidasesP01GM068036 · NIGMS · ALBERT EINSTEIN COL OF MED YESHIVA UNIV · PI CALLENDER, ROBERT · 2004 to 2018
$26.4M
TRANSITION STATE ANALYSIS OF ENZYMATIC REACTIONSR01GM041916 · NIGMS · YESHIVA UNIVERSITY · PI SCHRAMM, VERN L. · 1989 to 2023
$10.0M
Purine Pathways and Inhibitor Design in PlasmodiumR01AI049512 · NIAID · YESHIVA UNIVERSITY · PI SCHRAMM, VERN L. · 2002 to 2012
$4.8M
RICIN--MECHANISM, TRANSITION STATE AND INHIBITOR DESIGNR01CA072444 · NCI · YESHIVA UNIVERSITY · PI SCHRAMM, VERN L. · 1997 to 2011
$4.4M
TRANSITION STATE ANALYSIS OF ENZYMATIC REACTIONSR37GM041916 · NIGMS · YESHIVA UNIVERSITY · PI SCHRAMM, VERN L. · 1998 to 2007
$3.5M
Transition State Analogues as Modulators of DNA MethylationR01CA135405 · NCI · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI SCHRAMM, VERN L. · 2008 to 2018
$2.8M
NCI NIH HHS CA072444NCI NIH HHS CA135405NCI NIH HHS R01 CA072444NCI NIH HHS R01 CA135405NIAID NIH HHS AI049512NIAID NIH HHS R01 AI049512NIGMS NIH HHS GM41916NIGMS NIH HHS P01 GM068036NIGMS NIH HHS P01-GM068036NIGMS NIH HHS R01 GM041916NIGMS NIH HHS R37 GM041916
6 · The paper itself

Abstract

Experimental analysis of enzymatic transition-state structures uses kinetic isotope effects (KIEs) to report on bonding and geometry differences between reactants and the transition state. Computational correlation of experimental values with chemical models permits three-dimensional geometric and electrostatic assignment of transition states formed at enzymatic catalytic sites. The combination of experimental and computational access to transition-state information permits (a) the design of transition-state analogs as powerful enzymatic inhibitors, (b) exploration of protein features linked to transition-state structure, (c) analysis of ensemble atomic motions involved in achieving the transition state, (d) transition-state lifetimes, and (e) separation of ground-state (Michaelis complexes) from transition-state effects. Transition-state analogs with picomolar dissociation constants have been achieved for several enzymatic targets. Transition states of closely related isozymes indicate that the protein's dynamic architecture is linked to transition-state structure. Fast dynamic motions in catalytic sites are linked to transition-state generation. Enzymatic transition states have lifetimes of femtoseconds, the lifetime of bond vibrations. Binding isotope effects (BIEs) reveal relative reactant and transition-state analog binding distortion for comparison with actual transition states.

Indexed as

Protein ConformationAnimalsDrug DesignEnzyme InhibitorsEnzymesHumansIsotopesKineticsModels, MolecularMolecular StructureNucleosidesStatic ElectricityThermodynamicsEnzyme InhibitorsEnzymesIsotopesNucleosides

Identifiers

PMID21675920
PMCPMC5502542

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.