Effects of active site mutations in haemoglobin I fromLucina pectinata: a molecular dynamic study

Abstract

Haemoglobin I from Lucina pectinata is a monomeric protein consisting of 142 amino acids. Its active site contains a peculiar arrangement of phenylalanine residues (PheB10, PheCD1 and PheE11) and a distal Gln at position E7. Active site mutations at positions B10, E7 and E11 were performed in deoxy haemoglobin I (HbI), followed by 10 ns molecular dynamic simulations. The results showed that the mutations induced changes in domains far from the active site producing more flexible structures than the native HbI. Distance analyses revealed that the heme pocket amino acids at positions E7 and B10 are extremely sensitive to any heme pocket residue mutation. The high flexibility observed by the E7 position suggests an important role in the ligand binding kinetics in ferrous HbI, while both positions play a major role in the ligand stabilisation processes. Furthermore, our results showed that E11Phe plays a pivotal role in protein stability.

Hydrogen Sulfide and Hemeproteins: Knowledge and Mysteries

“…Once in the distal heme site, the flexibility of glutamine allows the ligand to bind rapidly to the ferric iron (24,43,(59)(60)(61)63). The gaseous ligand is stabilized in part by a hydrogen bonding interaction with glutamine (61,66).…”

Chemical Biology of H2S Signaling through Persulfidation

“…Another difference from human Hb, is the presence of phenylalanines in HbI that form a hydrophobic pocket around the sulfide. 401 It is unclear whether H 2 S release occurs via slow dissociation or by heme iron reduction. Introduction of positively charged substituents on the porphyrin ring changes the reactivity of metal porphyrins from simple binding of H 2 S to catalytic oxidation of H 2 S. 404 Hence, at low concentrations, H 2 S release could be due to its dissociation from the heme iron, while at high concentrations, heme reduction and H 2 S/hydropolysulfide delivery might predominate.…”

“…HbI exhibits a high association constant (k on = 2.3 × 10 5 M −1 s −1 ) and an unusually low dissociation constant (k off = 0.22 × 10 −3 s −1 ) for H 2 S, 390 which suggests the stabilization of distal sulfide ligand by the active site. 391,395,396,398,400,401 In human Hb, a histidine residue hydrogen bonds with the iron-bound sulfide. The corresponding residue in HbI is a glutamine, which has a flexible side chain.…”

“…Specialized hemoglobins that transport H 2 S are found in organisms that are adapted to life in sulfide-rich environments. The best-studied example of such a Hb is from the clam, Lucina pectinata (Figure B), ,− which lives in H 2 S-rich waters. The monomeric L. pectinata Hb hemoglobin I (HbI) transports H 2 S to symbiotic bacteria, which assimilate it and provide the host with a source of organic sulfur.…”

Structural Variations of Human Glucokinase Glu256Lys in MODY2 Condition Using Molecular Dynamics Study

“…In the same way, this study can provide the evidence for altered catalytic mechanism of each MODY2 mutated GK. Ramirez et al also studied in the same manner to identify the mutation inducing variations in the active site of Haemoglobin I from Lucina pectinata , and they analyzed the ligand binding kinetics that plays major role in the stabilization process of binding site [28]. …”