Abstract
For more than 100 years, myoglobin has been among the most extensively studied proteins. Since the first comprehensive review on myoglobin function as a dioxygen store by Millikan in 1939 and the discovery of its structure 50 years ago, multiple studies have extended our understanding of its occurrence, properties and functions. Beyond the two major roles, the storage and the facilitation of dioxygen diffusion, recent physiological studies have revealed that myoglobin acts as a potent scavenger of nitric oxide (NO(*)) representing a control system that preserves mitochondrial respiration. In addition, myoglobin may also protect the heart against reactive oxygen species (ROS), and, under hypoxic conditions, deoxygenated myoglobin is able to reduce nitrite to NO(*) leading to a downregulation of the cardiac energy status and to a decreased heart injury after reoxygenation. Thus, by controlling the NO(*) bioavailability via scavenging or formation, myoglobin serves as part of a sensitive dioxygen sensory system. In this review, the physiological relevance of these recent findings are delineated for pathological states where NO(*) and ROS bioavailability are known to be critical determinants for the outcome of the disease, e.g. ischemia/reperfusion injury. Detrimental and beneficial effects of the presence of myoglobin are discussed for various states of tissue oxygen tension within the heart and skeletal muscle. Furthermore, the impact of myoglobin on parasite infection, rhabdomyolysis, hindlimb and liver ischemia, angiogenesis and tumor growth are considered
Hendgen-Cotta UB, Flögel U, Kelm M, Rassaf T.
Department of Medicine, Division of Cardiology, Pulmonary Diseases and Angiology, University Hospital Düsseldorf, Düsseldorf, Germany.
Thursday
mass spectrometric comparison of the interactions of cisplatin and transplatin with myoglobin
Abstract
Mass spectrometric studies of the interactions of cisplatin and transplatin with myoglobin (Mb) provide information concerning interaction kinetics, Mb adduct identity, and cisplatin and transplatin binding sites on Mb.
Although the Mb–cisplatin interaction is faster than the Mb–transplatin interaction, monoadducts and diadducts were formed in both the interactions over 30 h. In order to locate the binding sites of cisplatin and transplatin on Mb, digests of free Mb, Mb–cisplatin and Mb–transplatin adducts were subjected to analysis by Fourier transform mass spectrometry (FT-MS). This analysis revealed that two fragment ions, 1313.275+ and 1316.685+, were obtained only from the Mb–cisplatin and Mb–transplatin adduct digests.
Tandem mass spectrometry (MS/MS and MS3) of the 1313.275+ and 1316.685+ ions indicate that these ions arise from [Pt(NH3)]2+ and [Pt(NH3)2]2+, respectively, bound to peptide His97-Gly153. The product-ion spectra of the MS/MS and MS3 analyses of the 1313.275+ ion indicate a common binding site of cisplatin and transplatin on His116-His119 residues. The interactions of cisplatin and transplatin with a dipeptide His-Ser and the three dimensional (3D) structure of native Mb suggest that cisplatin and transplatin coordinate to His116 and His119.
Ting Zhaoa and Fred L. King, a,
a C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV 26506-6045, USA
Mass spectrometric studies of the interactions of cisplatin and transplatin with myoglobin (Mb) provide information concerning interaction kinetics, Mb adduct identity, and cisplatin and transplatin binding sites on Mb.
Although the Mb–cisplatin interaction is faster than the Mb–transplatin interaction, monoadducts and diadducts were formed in both the interactions over 30 h. In order to locate the binding sites of cisplatin and transplatin on Mb, digests of free Mb, Mb–cisplatin and Mb–transplatin adducts were subjected to analysis by Fourier transform mass spectrometry (FT-MS). This analysis revealed that two fragment ions, 1313.275+ and 1316.685+, were obtained only from the Mb–cisplatin and Mb–transplatin adduct digests.
Tandem mass spectrometry (MS/MS and MS3) of the 1313.275+ and 1316.685+ ions indicate that these ions arise from [Pt(NH3)]2+ and [Pt(NH3)2]2+, respectively, bound to peptide His97-Gly153. The product-ion spectra of the MS/MS and MS3 analyses of the 1313.275+ ion indicate a common binding site of cisplatin and transplatin on His116-His119 residues. The interactions of cisplatin and transplatin with a dipeptide His-Ser and the three dimensional (3D) structure of native Mb suggest that cisplatin and transplatin coordinate to His116 and His119.
Ting Zhaoa and Fred L. King, a,
a C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV 26506-6045, USA
Subscribe to:
Posts (Atom)