Crystal structures and calorimetry reveal catalytically relevant binding mode of coproporphyrin and coproheme in coproporphyrin ferrochelatase.

07:00 EST 3rd December 2019 | BioPortfolio

Summary of "Crystal structures and calorimetry reveal catalytically relevant binding mode of coproporphyrin and coproheme in coproporphyrin ferrochelatase."

Coproporphyrin ferrochelatases (CpfCs, EC insert ferrous iron into coproporphyrin III yielding coproheme. CpfCs are utilized by prokaryotic, mainly monoderm (Gram-positive) bacteria within the recently detected coproporphyrin-dependent heme biosynthesis pathway. Here we present a comprehensive study on CpfC from Listeria monocytogenes (LmCpfC) including the first crystal structure of a coproheme-bound CpfC. Comparison of crystal structures of apo-LmCpfC and coproheme-LmCpfC allowed identification of structural rearrangements and of amino acids involved in tetrapyrrole macrocycle and Fe binding. Differential scanning calorimetry of apo-, coproporphyrin III- and coproheme-LmCpfC underline the pronounced non-covalent interaction of both coproporphyrin and coproheme with the protein (ΔT = 11 °C compared to apo-LmCpfC) which includes the propionates (p2, p4, p6, p7) and the amino acids Arg29, Arg45, Tyr46, Ser53 and Tyr124. Furthermore, the thermodynamics and kinetics of coproporphyrin III and coproheme binding to apo-LmCpfC is presented as well as the kinetics of insertion of ferrous iron into coproporphyrin III-LmCpfC that immediately leads to formation of ferric coproheme-LmCpfC (k /K = 4.7 × 10 M s ). We compare the crystal structure of coproheme-LmCpfC with available structures of CpfCs with artificial tetrapyrrole macrocycles and discuss our data on substrate binding, iron insertion and substrate release in the context of the coproporphyrin-dependent heme biosynthesis pathway.


Journal Details

This article was published in the following journal.

Name: The FEBS journal
ISSN: 1742-4658


DeepDyve research library

PubMed Articles [18287 Associated PubMed Articles listed on BioPortfolio]

Functional characterisation of two ferric-ion coordination modes of TtFbpA, the periplasmic subunit of an ABC-type iron transporter from Thermus thermophilus HB8.

The ferric ion binding protein A of Thermus thermophilus HB8 (TtFbpA) is the periplasmic subunit of an ABC-type iron transporter. Two Fe3+-bound crystal structures at pH 5.5 and pH 7.5 and one apo str...

Atomic-resolution crystal structures of the immune protein conglutinin from cow reveal specific interactions of its binding site with -acetylglucosamine.

Bovine conglutinin is an immune protein that is involved in host resistance to microbes and parasites and interacts with complement component iC3b, agglutinates erythrocytes, and neutralizes influenza...

Crystal and Solution Structures of Human Oncoprotein Musashi-2 N-terminal RNA Recognition Motif 1.

Musashi-2 (MSI2) belongs to Musashi family of RNA binding proteins. Like Musashi-1 (MSI1), it is overexpressed in a variety of cancers and is a promising therapeutic target. Both MSI proteins contain ...

Structures of Hsp90α and Hsp90β bound to a purine-scaffold inhibitor reveal an exploitable residue for drug selectivity.

Hsp90α and Hsp90β are implicated in a number of cancers and neurodegenerative disorders but the lack of selective pharmacological probes confounds efforts to identify their individual roles. Here, w...

Plasticity at the DNA recognition site of the MeCP2 mCG-binding domain.

MeCP2 is an abundant protein, involved in transcriptional repression by binding to CG and non-CG methylated DNA. However, MeCP2 might also function as a transcription activator as MeCP2 is found bound...

Clinical Trials [3285 Associated Clinical Trials listed on BioPortfolio]

The ICALIC International Multicentric Study

This study will evaluate the ease of use of the new calorimeter (Quark RMR 2.0 (COSMED, Italy)) in intensive care unit (ICU) patients compared to currently used calorimeters (i.e. Quark RM...

Co-crystal E-58425 vs Tramadol and Celecoxib for Moderate to Severe Acute Pain After Bunionectomy. Phase III Clinical Trial.

This is a Phase 3, randomized, double-blind, controlled, parallel-group, multicenter clinical trial with co-crystal E-58425 compared to tramadol, to celecoxib, and to placebo. The primary ...

Using Indirect Calorimetry for Liver Transplants Patients

Although predicted REE calculated using the Penn state 1988 method agreed (ICC 0.61, p=0.00014) with the measured REE, all three predictive equations had a fixed bias and appeared to be in...

Feeding With Indirect Calorimetry and Cycling in the Elderly

The aim of this study is to evaluate the effect of early exercise by cycle ergometry and early targeted feeding in reducing muscle atrophy and improve functional outcomes in the older crit...

Use of Indirect Calorimetry in Obesity

The investigators will retrospectively analyze and compare data of 2 groups of overweight and obese patients: subjects who followed a diet based on Resting Energy Expenditure (REE) measure...

Medical and Biotech [MESH] Definitions

A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.

The use of a quartz crystal microbalance for measuring weights and forces in the micro- to nanogram range. It is used to study the chemical and mechanical properties of thin layers, such as polymer coatings and lipid membranes; and interactions between molecues.

Patterns (real or mathematical) which look similar at different scales, for example the network of airways in the lung which shows similar branching patterns at progressively higher magnifications. Natural fractals are self-similar across a finite range of scales while mathematical fractals are the same across an infinite range. Many natural, including biological, structures are fractal (or fractal-like). Fractals are related to "chaos" (see NONLINEAR DYNAMICS) in that chaotic processes can produce fractal structures in nature, and appropriate representations of chaotic processes usually reveal self-similarity over time.

Catalytically active enzymes that are formed by the combination of an apoenzyme (APOENZYMES) and its appropriate cofactors and prosthetic groups.

Calculation of the energy expenditure in the form of heat production of the whole body or individual organs based on respiratory gas exchange.

Quick Search

DeepDyve research library

Relevant Topic

Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...

Searches Linking to this Article