About

Judith P. Klinman, born in 1941, is a Professor of the Graduate School and a Chancellor's Professor in the Department of Chemistry at the University of California, Berkeley. She holds an A.B. degree from the University of Pennsylvania (1962) and a Ph.D. in Physical-Organic Chemistry from the same institution (1966). Her postdoctoral work was conducted at the Weizmann Institute of Science, and she has served as a Research Scientist at the Institute for Cancer Research in Philadelphia from 1968 to 1978. Klinman's research focuses on biochemistry, biophysical, bioorganic, and bioinorganic chemistry, with particular emphasis on enzyme catalysis. Her laboratory investigates fundamental aspects of enzyme catalysis, including reaction barrier shapes at enzyme active sites and the contribution of protein dynamics to bond cleavage processes. A significant aspect of her work involves detecting and quantifying hydrogen tunneling in enzymatic reactions, providing insights into the role of protein and heavy atom motions in promoting C-H activation via tunneling. She has contributed to the discovery of a new class of proteins called quino-enzymes, which contain their cofactors within the protein polypeptide chain, such as TPQ and LTQ, and studies their biogenesis and enzyme turnover. Klinman’s research also explores how proteins catalyze the activation of molecular oxygen while avoiding oxidative damage, employing methodologies like site-specific mutagenesis, spectroscopy, and isotope effects to develop fundamental principles across enzyme classes.

Research topics

• Chemistry
• Biochemistry
• Organic chemistry
• Crystallography
• Stereochemistry
• Physics
• Atomic physics
• Inorganic chemistry
• Nuclear physics
• Combinatorial chemistry
• Mathematics

Selected publications

• Computational Method for the Detection of Communication Pathways in Enzymes that Correlate with Experimentally Defined Thermal Activation Networks

  The Journal of Physical Chemistry Letters · 2026-05-01

  articleOpen accessSenior author

  Enzyme catalysis has been shown to depend on distal pathways that channel thermal energy from solvent to the active site. Here, we develop a method to compute these pathways using soybean lipoxygenase (SLO), an extensively studied prototype for dynamical initiation of C-H activation. Experiments with SLO have previously identified a cone-shaped network connecting a surface loop residue (Gln322) to a buried active site residue, Leu546, positioned adjacent to the reactive bond of substrate. We introduce microsecond molecular dynamics and a correlated motion-based protocol to obtain an atomistic analysis of this long-range communication. The developed approach also enables systematic screening of communication between active site-specific residues that directly contact bound substrate and surface-exposed residues on the protein-solvent interface. In addition to providing deeper molecular insight into the experimentally mapped thermal energy network in SLO, this methodology has the potential to discover communication trends across diverse enzyme families. The simulations recover the experimentally demonstrated thermal initiation loop and the Leu546-directed cone in SLO, exclude the negative-control Ser596, and explain the preference for Leu546 over Leu754, a second active site residue in contact with bound substrate. Mutational analysis further reveals the impact of single-site mutations on the network preference between Leu546 and Leu754. These results unify experiments and computation, corroborate an anisotropic channeling of thermal energy in SLO, and establish a general framework for computing site-specific distal intraprotein pathways capable of the thermal initiation of enzyme function.

  PublisherOA PDFDOI

• Identification of Scaffold Specific Energy Transfer Networks in the Enthalpic Activation of Orotidine 5’-Monophosphate Decarboxylase

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-01-29 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Abstract Orotidine 5’-monophosphate decarboxylase (OMPDC) is one of the most efficient enzyme systems studied, enhancing the decarboxylation of OMP to uridine 5’-monophosphate (UMP) by ca. 17 orders of magnitude, primarily by reducing the enthalpy of activation by ca. 28 kcal/mol. Despite a substantial reduction in activation enthalpy, OMPDC requires 15 kcal/mol of activation energy post- ES complex formation. This study investigates the physical basis of how thermal energy from solvent collisions is directed into the active site of enzyme to enable efficient thermal activation of the reaction. Comparative study of temperature-dependent hydrogen-deuterium exchange mass spectrometry (TDHDX) for WT and mutant forms of enzymes has recently been shown to uncover site specific protein networks for thermal energy transfer from solvent to enzyme active sites. In this study, we interrogate region-specific changes in the enthalpic barrier for local protein flexibility using a native OMPDC from Methanothermobacter thermautotrophicus (Mt-OMPDC) and a single site variant (Leu123Ala) that alters the activation enthalpy for catalytic turnover. The data obtained implicate four spatially resolved, thermally sensitive networks that originate at different protein/solvent interfaces and terminate at sites surrounding the substrate near the substrate phosphate-binding region (R203), the substrate- ribose binding region (K42), and a reaction enhancing loop5 (S127). These are proposed to act synergistically, transiently optimizing the position and electrostatics of the reactive carboxylate of the substrate to facilitate activated complex formation. The uncovered complexity of thermal activation networks in Mt-OMPDC distinguishes this enzyme from other members of the TIM barrel family previously investigated by TDHDX. The new findings extend the essential role of protein scaffold dynamics in orchestrating enzyme activity, with broad implications for the design of highly efficient biocatalysts.

  PublisherDOI

• BPS2025 - Computational analysis of solvent to active site thermal energy transfer networks in lipoxygenase

  Biophysical Journal · 2025-02-01

  articleSenior author
  PublisherDOI

• BPS2025 - Unraveling temperature-induced conformational dynamics in htADH using TDHDX-MS

  Biophysical Journal · 2025-02-01

  articleSenior author
  PublisherDOI

• BPS2025 - Covalent attachment of site-specific photoactive heat transfer probes to test models of long-range, local heating in soybean lipoxygenase

  Biophysical Journal · 2025-02-01

  articleSenior author
  PublisherDOI

• BPS2025 - Revealing site-specific thermal networks in OMP-decarboxylase: Drivers of enthalpic barrier crossing and catalysis

  Biophysical Journal · 2025-02-01

  articleSenior author
  PublisherDOI

• BPS2025 - Light-induced changes in protein dynamics of pigeon CRY4: Insights into magnetoreception

  Biophysical Journal · 2025-02-01

  articleSenior author
  PublisherDOI

• BPS2025 - Light-induced changes in protein dynamics of pigeon CRY4: Insights into magnetoreception

  Biophysical Journal · 2025-02-01

  articleSenior author
  PublisherDOI

• Correlated Motion-Based Residue Network Analysis Reveals the Distal Thermal Activation in Soybean Lipoxygenase

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-09 · 1 citations

  articleOpen accessSenior authorCorresponding

  Enzyme catalysis has been shown to depend on distal pathways that channel thermal energy from solvent to the active site. In soybean lipoxygenase (SLO), experiments identified a cone-shaped network connecting loop residue Gln322 to Leu546 but not Leu754 in the active site. Here, microsecond molecular dynamics and a correlated motion-based protocol provide an atomistic analysis of such long-range communication. The developed approach enables systematic screening of communication between active site-specific residues that directly contact bound substrate and surface-exposed residues on the protein-solvent interface. In doing so, it provides a deeper molecular insight into experimentally mapped networks by resolving communication trends across diverse conformational ensembles. The simulations recover the experimentally demonstrated thermal initiation loop and the Leu546-directed cone in SLO, exclude the negative-control Ser596, and explain the preference for Leu546 over Leu754 through shorter, more correlated helical pathways. Mutational analysis further reveals the impact of single-site mutations on the network preference between Leu546 and Leu754. These results unify experiments and computation, corroborating an anisotropic channeling of thermal energy in SLO and establishing a general framework for computing distal intra-protein pathways that may enable the thermal activation of enzyme function.

  PublisherDOI

• BPS2025 - Revealing site-specific thermal networks in OMP-decarboxylase: Drivers of enthalpic barrier crossing and catalysis

  Biophysical Journal · 2025-02-01

  articleSenior author
  PublisherDOI

Recent grants

• NIH Grant R01GM025765

  NIH · $7.9M · 2016

• NIH Grant R01GM039296

  NIH · $8.8M · 2017

• NIH Grant R37GM025765

  NIH · $2.4M · 2000

• Looking in New Directions for Origins and Cryptic Mechanisms of Enzyme Catalysis

  NIH · $7.5M · 2016–2027

• Linking Protein Dynamics to Hydrogen Tunneling

  NSF · $1.2M · 2005–2011

Frequent coauthors

• Judith Bond

  112 shared

• Bettie Sue Siler Masters

  Duke Medical Center

  112 shared

• Robert D. Wells

  112 shared

• Anthony T. Iavarone

  QB3

  73 shared

• Adam R. Offenbacher

  East Carolina University

  57 shared

• Shenshen Hu

  University of California, Berkeley

  42 shared

• Joann Sanders–Loehr

  29 shared

• Jianyu Zhang

  Guangdong Provincial People's Hospital

  28 shared

Awards & honors

• Member ASBMB
• Member ACS
• Member AAAS
• Member NAS
• Member APS