Influence of heme environment structure on dioxygen affinity for the dual function Amphitrite ornata hemoglobin/dehaloperoxidase. Insights into the evolutional structure–function adaptations

2014 ◽  
Vol 545 ◽  
pp. 108-115 ◽  
Author(s):  
Shengfang Sun ◽  
Masanori Sono ◽  
Chunxue Wang ◽  
Jing Du ◽  
Lukasz Lebioda ◽  
...  
Keyword(s):  
Structure Function ◽  
Dual Function ◽  
Amphitrite Ornata

Structures of K42N and K42Y sperm whale myoglobins point to an inhibitory role of distal water in peroxidase activity

2014 ◽  
Vol 70 (11) ◽  
pp. 2833-2839 ◽  
Author(s):  
Chunxue Wang ◽  
Leslie L. Lovelace ◽  
Shengfang Sun ◽  
John H. Dawson ◽  
Lukasz Lebioda
Keyword(s):  
Peroxidase Activity ◽  
Physiological Role ◽  
Sperm Whale ◽  
Reaction Rates ◽  
Heme Iron ◽  
Oxygen Storage ◽  
Dual Function ◽  
Amphitrite Ornata ◽  
Coordinated Water

Sperm whale myoglobin (Mb) functions as an oxygen-storage protein, but in the ferric state it possesses a weak peroxidase activity which enables it to carry out H2O2-dependent dehalogenation reactions. Hemoglobin/dehaloperoxidase fromAmphitrite ornata(DHP) is a dual-function protein represented by two isoproteins DHP A and DHP B; its peroxidase activity is at least ten times stronger than that of Mb and plays a physiological role. The `DHP A-like' K42Y Mb mutant (K42Y) and the `DHP B-like' K42N mutant (K42N) were engineered in sperm whale Mb to mimic the extended heme environments of DHP A and DHP B, respectively. The peroxidase reaction rates increased ∼3.5-fold and ∼5.5-fold in K42Y and K42NversusMb, respectively. The crystal structures of the K42Y and K42N mutants revealed that the substitutions at position 42 slightly elongate not only the distances between the distal His55 and the heme iron but also the hydrogen-bonding distances between His55 and the Fe-coordinated water. The enhanced peroxidase activity of K42Y and K42N thus might be attributed in part to the weaker binding of the axial water molecule that competes with hydrogen peroxide for the binding site at the heme in the ferric state. This is likely to be the mechanism by which the relationship `longer distal histidine to Fe distance – better peroxidase activity', which was previously proposed for heme proteins by Matsuiet al.(1999) (J. Biol. Chem.274, 2838–2844), works. Furthermore, positive cooperativity in K42N was observed when its dehaloperoxidase activity was measured as a function of the concentration of the substrate trichlorophenol. This serendipitously engineered cooperativity was rationalized by K42N dimerization through the formation of a dityrosine bond induced by excess H2O2.

Linalool Effect on HepG2 cells: Structure Function Relation

Planta Medica ◽  
2011 ◽  
Vol 77 (12) ◽  
Author(s):  
J Usta ◽  
K Racha ◽  
K Boushra ◽  
S Shatha ◽  
B Yolla ◽  
...  
Keyword(s):  
Structure Function ◽  
Hepg2 Cells ◽  
Function Relation

TGF-β: Structure, Function, and Formation

1993 ◽  
Vol 70 (01) ◽  
pp. 177-179 ◽  
Author(s):  
Daniel B Rifkin ◽  
Soichi Kojima ◽  
Mayumi Abe ◽  
John G Harpel
Keyword(s):  
Structure Function

Clues for Understanding the Structure and Function of a Prototypic Human Integrin: The Platelet Glycoprotein IIb/IIIa Complex

1994 ◽  
Vol 72 (01) ◽  
pp. 001-015 ◽  
Author(s):  
Juan J Calvete
Keyword(s):  
Structure Function ◽  
Thrombus Formation ◽  
Platelet Glycoprotein ◽  
Primary Role ◽  
Clot Retraction ◽  
Inhibitory Peptide ◽  
Rgd Sequence ◽  
Platelet Receptor ◽  
Adhesive Proteins ◽  
And Function

SummaryThe glycoprotein (GP) IIb/IIIa, a Ca2+-dependent heterodimer, is the major integrin on the platelet plasma membrane. On resting platelets GPIIb/IIIa is maintained in an inactive conformation and serves as a low affinity adhesion receptor for surface-coated fibrinogen, whereas upon platelet activation signals within the cytoplasma alter the receptor function of GPIIb/IIIa (inside-out signalling), which undergoes a measurable conformational change within its exoplasmic domains, and becomes a competent receptor for soluble fibrinogen and some other RGD sequence-containing plasma adhesive proteins. Upon ligand binding, further structural alterations trigger the association of receptor-occupied GPIIb/IIIa complexes with themselves within the plane of the membrane. The simultaneous binding of dimeric fibrinogen molecules to GPIIb/IIIa clusters on adjacent platelets leads to platelet aggregation, which promotes attachment of fibrinogen-GPIIb/IIIa clusters to the cytoskeleton (outside-in signalling). This, in turn, provides the necessary physical link for clot retraction to occur, and generates a cascade of intracellular biochemical reactions which result in the formation of a multiprotein signalling complex at the cytoplasmic domains of GPIIb/IIIa. Glycoprotein IMIIa, also called αIIbβ3 in the integrin nomenclature, plays thus a primary role in both platelet adhesion and thrombus formation at the site of vascular injury. In addition, the human glycoprotein Ilb/IIIa complex is the most thoroughly studied integrin receptor, its molecular biology and major features of its primary structure having been elucidated mainly during the last six years. Furthermore, localization of functionally relevant monoclonal antibody epitopes, determination of the cross-linking sites of inhibitory peptide ligands, proteolytic dissection of the isolated integrin, and analysis of natural and artificial GPIIb/IIIa mutants have recently provided a wealth of information regarding structure-function relationships of human GPIIb/IIIa. The aim of this review is to summarize these many structural and functional data in the perspective of an emerging model. Although most of the interpretations based on structural elements of this initial biochemical model require independent confirmation, they may help us to understand the structure-function relationship of this major platelet receptor, and of other members of the integrin superfamily, as well as to perform further investigations in order to test current hypotheses.

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