Andreas Heine

Flexible adaptations in the structure of the tRNA-modifying enzyme tRNA-guanine transglycosylase and their implications for substrate selectivity, reaction mechanism and structure-based drug design.

An old target revisited: two new privileged skeletons and an unexpected binding mode for HIV-protease inhibitors.

Hydroxyethylene sulfones as a new scaffold to address aspartic proteases: design, synthesis, and structural characterization.

Unexpected novel binding mode of pyrrolidine-based aspartyl protease inhibitors: design, synthesis and crystal structure in complex with HIV protease.

Crystal structures of tRNA-guanine transglycosylase (TGT) in complex with novel and potent inhibitors unravel pronounced induced-fit adaptations and suggest dimer formation upon substrate binding.

Saccharin inhibits carbonic anhydrases: possible explanation for its unpleasant metallic aftertaste.

Thermodynamic inhibition profile of a cyclopentyl and a cyclohexyl derivative towards thrombin: the same but for different reasons.

Glutamate versus glutamine exchange swaps substrate selectivity in tRNA-guanine transglycosylase: insight into the regulation of substrate selectivity by kinetic and crystallographic studies.

Structure-guided design of C2-symmetric HIV-1 protease inhibitors based on a pyrrolidine scaffold.

Structural and kinetic analysis of pyrrolidine-based inhibitors of the drug-resistant Ile84Val mutant of HIV-1 protease.

Targeting the open-flap conformation of HIV-1 protease with pyrrolidine-based inhibitors.

Achiral oligoamines as versatile tool for the development of aspartic protease inhibitors.

Crystal structure analysis and in silico pKa calculations suggest strong pKa shifts of ligands as driving force for high-affinity binding to TGT.

How to replace the residual solvation shell of polar active site residues to achieve nanomolar inhibition of tRNA-guanine transglycosylase.

Fragment-based lead discovery: screening and optimizing fragments for thermolysin inhibition.

Structure and substrate docking of a hydroxy(phenyl)pyruvate reductase from the higher plant Coleus blumei Benth.

Bidentate Zinc chelators for alpha-carbonic anhydrases that produce a trigonal bipyramidal coordination geometry.

Stereo- and regioselective azide/alkyne cycloadditions in carbonic anhydrase II via tethering, monitored by crystallography and mass spectrometry.

Two solutions for the same problem: multiple binding modes of pyrrolidine-based HIV-1 protease inhibitors.

Structural analysis of coniferyl alcohol 9-O-methyltransferase from Linum nodiflorum reveals a novel active-site environment.

Investigation of specificity determinants in bacterial tRNA-guanine transglycosylase reveals queuine, the substrate of its eucaryotic counterpart, as inhibitor.

High resolution crystal structure of Clostridium propionicum β-alanyl-CoA:ammonia lyase, a new member of the "hot dog fold" protein superfamily.

Chasing protons: how isothermal titration calorimetry, mutagenesis, and pKa calculations trace the locus of charge in ligand binding to a tRNA-binding enzyme.

Beyond affinity: enthalpy-entropy factorization unravels complexity of a flat structure-activity relationship for inhibition of a tRNA-modifying enzyme.

Tracing binding modes in hit-to-lead optimization: chameleon-like poses of aspartic protease inhibitors.

Six Biophysical Screening Methods Miss a Large Proportion of Crystallographically Discovered Fragment Hits: A Case Study.

Structures of endothiapepsin-fragment complexes from crystallographic fragment screening using a novel, diverse and affordable 96-compound fragment library.

High-Throughput Crystallography: Reliable and Efficient Identification of Fragment Hits.

Occupying a flat subpocket in a tRNA-modifying enzyme with ordered or disordered side chains: Favorable or unfavorable for binding?

A False-Positive Screening Hit in Fragment-Based Lead Discovery: Watch out for the Red Herring.

Price for Opening the Transient Specificity Pocket in Human Aldose Reductase upon Ligand Binding: Structural, Thermodynamic, Kinetic, and Computational Analysis.

Charges Shift Protonation: Neutron Diffraction Reveals that Aniline and 2-Aminopyridine Become Protonated Upon Binding to Trypsin.

Soaking suggests "alternative facts": Only co-crystallization discloses major ligand-induced interface rearrangements of a homodimeric tRNA-binding protein indicating a novel mode-of-inhibition.

Homodimer Architecture of QTRT2, the Noncatalytic Subunit of the Eukaryotic tRNA-Guanine Transglycosylase.

Paradoxically, Most Flexible Ligand Binds Most Entropy-Favored: Intriguing Impact of Ligand Flexibility and Solvation on Drug-Kinase Binding.

Swapping Interface Contacts in the Homodimeric tRNA-Guanine Transglycosylase: An Option for Functional Regulation.

Sugar Acetonides are a Superior Motif for Addressing the Large, Solvent-Exposed Ribose-33 Pocket of tRNA-Guanine Transglycosylase.

On the Implication of Water on Fragment-to-Ligand Growth in Kinase Binding Thermodynamics.

Intriguing role of water in protein-ligand binding studied by neutron crystallography on trypsin complexes.

Strategies for Late-Stage Optimization: Profiling Thermodynamics by Preorganization and Salt Bridge Shielding.

Surprising Non-Additivity of Methyl Groups in Drug-Kinase Interaction.

Conformational Changes in Alkyl Chains Determine the Thermodynamic and Kinetic Binding Profiles of Carbonic Anhydrase Inhibitors.

The Influence of Varying Fluorination Patterns on the Thermodynamics and Kinetics of Benzenesulfonamide Binding to Human Carbonic Anhydrase II.

A Proof-of-Concept Fragment Screening of a Hit-Validated 96-Compounds Library against Human Carbonic Anhydrase II.

F2X-Universal and F2X-Entry: Structurally Diverse Compound Libraries for Crystallographic Fragment Screening.

Fragment Binding to Kinase Hinge: If Charge Distribution and Local pK Shifts Mislead Popular Bioisosterism Concepts.

Two Methods, One Goal: Structural Differences between Cocrystallization and Crystal Soaking to Discover Ligand Binding Poses.

The Importance of Charge in Perturbing the Aromatic Glue Stabilizing the Protein-Protein Interface of Homodimeric tRNA-Guanine Transglycosylase.

How a Fragment Draws Attention to Selectivity Discriminating Features between the Related Proteases Trypsin and Thrombin.