Related Experiment Video
Updated: Jul 5, 2026

Structure-Guided Design and Development of Novel Cyclophilin A Inhibitors and Ganoderiol-F Derivatives: An In-Silico Approach
Published on: June 23, 2026
Ligand preference and orientation in b- and c-type heme-binding proteins
Christian Fufezan1, Jun Zhang, M R Gunner
1Physics Department, City College of New York, New York, New York 10031, USA. christian@fufezan.net
Investigating heme ligands in designed proteins reveals distinct orientation preferences for b- and c-type hemes. Covalent attachment influences c-type heme ligand orientation, unlike b-type hemes.
Area of Science:
- Biochemistry
- Structural Biology
- Protein Design
Background:
- Heme incorporation into proteins is common in designed systems.
- The role of heme ligand type and orientation in protein function remains under investigation.
Purpose of the Study:
- To compare and contrast design features of natural b- and c-type heme-binding proteins.
- To investigate the influence of heme ligand type and orientation on protein structure and energetics.
Main Methods:
- Analysis of nonredundant (87) and redundant (1503) protein structure datasets.
- Comparison of ligation motifs and ligand orientations between b- and c-type hemes.
- Molecular mechanics calculations to assess energetic constraints.
Main Results:
- Histidine is the predominant heme ligand.
- C-type hemes show higher His-Met occurrence (16.4%) vs. b-type (1.4%); b-type hemes exhibit more exchangeable ligands (67.6%) vs. c-type (9.9%).
- C-type heme histidine ligands exhibit asymmetric orientation due to covalent attachment, unlike evenly distributed b-type heme ligands.
Conclusions:
- Covalent linkage significantly constrains c-type heme ligand orientation.
- Ligand orientation is not primarily dictated by electrostatic interactions with heme propionates.
- Observed ligand orientations support energetic constraints relevant for protein design.
More Related Videos
11:04Ion Mobility-Mass Spectrometry Techniques for Determining the Structure and Mechanisms of Metal Ion Recognition and Redox Activity of Metal Binding Oligopeptides
Published on: September 7, 2019
10:44Fluorescence Anisotropy as a Tool to Study Protein-protein Interactions
Published on: October 21, 2016
Related Concept Videos
Ligand Binding Sites
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Ligand Binding Sites
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Metal-Ligand Bonds
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
Ligand Binding and Linkage
Ligand Binding and Linkage
The Equilibrium Binding Constant and Binding Strength