Comprehensive structural analysis of the open and closed conformations of Theileria annulata enolase by molecular modelling and docking

Mutlu, Özal; Yakarsonmez, Sinem; Sarıyer, Emrah; Danış, Özkan; Yüce‐Dursun, Başak; Topuzoğulları, Murat; Akbulut, Ekrem; Turgut-Balık, Dilek

doi:10.1016/j.compbiolchem.2016.06.002

Cited by 7 publications

(2 citation statements)

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“…Plasminogen contains five kringle domains (K1-K5) which mediate its binding to enolase with accessible carboxyl-terminal or internal lysine residues [14]. Moreover, enolase has an internal motif ( 248 FYDKERKVY 256 ) responsible for plasminogen binding, which has been characterized in enolases from Streptococcus pneumonia [15,16], as well as from other microorganisms, such as Streptococcus iniae [8], Leishmania mexicana [17], Bartonella henselae [6], Plasmodium [18], and Theileria annulata [19].…”

Section: Introductionmentioning

confidence: 99%

Structural Characterization of Haemophilus influenzae Enolase and Its Interaction with Human Plasminogen by In Silico and In Vitro Assays

et al. 2021

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Haemophilus influenzae is the causal agent of invasive pediatric diseases, such as meningitis, epiglottitis, pneumonia, septic arthritis, pericarditis, cellulitis, and bacteremia (serotype b). Non-typeable H. influenzae (NTHi) strains are associated with localized infections, such as otitis media, conjunctivitis, sinusitis, bronchitis, and pneumonia, and can cause invasive diseases, such as as meningitis and sepsis in immunocompromised hosts. Enolase is a multifunctional protein and can act as a receptor for plasminogen, promoting its activation to plasmin, which leads to the degradation of components of the extracellular matrix, favoring host tissue invasion. In this study, using molecular docking, three important residues involved in plasminogen interaction through the plasminogen-binding motif (251EFYNKENGMYE262) were identified in non-typeable H. influenzae enolase (NTHiENO). Interaction with the human plasminogen kringle domains is conformationally stable due to the formation of four hydrogen bonds corresponding to enoTYR253-plgGLU1 (K2), enoTYR253-plgGLY310 (K3), and enoLYS255-plgARG471/enoGLU251-plgLYS468 (K5). On the other hand, in vitro assays, such as ELISA and far-western blot, showed that NTHiENO is a plasminogen-binding protein. The inhibition of this interaction using polyclonal anti-NTHiENO antibodies was significant. With these results, we can propose that NTHiENO–plasminogen interaction could be one of the mechanisms used by H. influenzae to adhere to and invade host cells.

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Section: Introductionmentioning

confidence: 99%

Structural Characterization of Haemophilus influenzae Enolase and Its Interaction with Human Plasminogen by In Silico and In Vitro Assays

et al. 2021

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“…Crystallographic data also indicate differences in loop conformations when the enzyme is bound to 2PG versus PEP . Several computational studies of yeast enolase or homologous enzymes have been conducted in an effort to understand the structure and catalytic mechanism. − In particular, mixed quantum mechanical/molecular mechanical (QM/MM) calculations have been performed to study the dehydration reaction catalyzed by yeast enolase. , Molecular dynamics (MD) simulations have also been performed to investigate the structural flexibility and protein interactions. − , …”

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confidence: 99%

Substrate-to-Product Conversion Facilitates Active Site Loop Opening in Yeast Enolase: A Molecular Dynamics Study

Hammes‐Schiffer

2019

ACS Catal.

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Yeast enolase serves as a prototype for metalloenzymes with labile, catalytically active site metal ions and is important for glycolysis and fermentation processes. Herein, microsecond molecular dynamics simulations of the protein–substrate and protein–product complexes are conducted to elucidate the mechanism of the opening of catalytically important active site loops. These simulations indicate that conversion of substrate to product is accompanied by diminished metal coordination and hydrogen-bonding interactions, as well as enhanced loop flexibility. Moreover, free-energy simulations show that the loop opening is endergonic when substrate is bound but exergonic when product is bound. Thus, the conversion to product weakens the association of the loop with the ligand and binding site, thereby facilitating the loop opening after catalysis and enabling product release. These insights about active site loop motions in enzyme catalysis may be useful in guiding enzyme design efforts.

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Discovery and evaluation of inhibitory activity and mechanism of arylcoumarin derivatives on Theileria annulata enolase by in vitro and molecular docking studies

et al. 2019

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Comprehensive structural analysis of the open and closed conformations of Theileria annulata enolase by molecular modelling and docking

Cited by 7 publications

References 55 publications

Structural Characterization of Haemophilus influenzae Enolase and Its Interaction with Human Plasminogen by In Silico and In Vitro Assays

Structural Characterization of Haemophilus influenzae Enolase and Its Interaction with Human Plasminogen by In Silico and In Vitro Assays

Substrate-to-Product Conversion Facilitates Active Site Loop Opening in Yeast Enolase: A Molecular Dynamics Study

Discovery and evaluation of inhibitory activity and mechanism of arylcoumarin derivatives on Theileria annulata enolase by in vitro and molecular docking studies

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