The Crystal Structure of Wild-Type Growth Hormone at 2.5 a Resolution

Chantalat, L.; Jones, N.D.; Körber, F.; Navaza, Jorge; Pavlovsky, A.G.

doi:10.2174/092986650202220524124754

Cited by 56 publications

(16 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The SAXS curves were buffer subtracted and analyzed with the SAS Data analysis module from the ATSAS 2.5.0 package, and the deduced values are found in Table . A rigid body refinement using a HSA model in complex with octadecanoic acid and two growth hormone molecules was applied in the ATSAS SASREF module using 15 Å distance constraints from residue 101 of growth hormone to residues 209 (FA6) and 502 (FA5) of HSA. The SAXS data and models are deposited in the small-angle scattering biological data bank () with the accession codes listed in Table .…”

Section: Materials and Methodsmentioning

confidence: 99%

Identification of Binding Sites on Human Serum Albumin for Somapacitan, a Long-Acting Growth Hormone Derivative

et al. 2020

View full text Add to dashboard Cite

Somapacitan, a human growth hormone derivative that binds reversibly to albumin, was investigated for human serum albumin (HSA) and HSA domain binding. Isothermal titration calorimetry (ITC) binding profiles showed high-affinity binding (∼100–1000 nM) of one somapacitan molecule and low-affinity binding (∼1000–10000 nM) of one to two somapacitan molecules to HSA. The high-affinity site was identified in HSA domain III using size exclusion chromatography (SEC) and ITC. SEC studies showed that the neonatal Fc receptor shields one binding site for somapacitan, indicating its position in domain III. A crystal structure of somapacitan in complex with HSA optimized for neonatal Fc receptor binding, having four amino acid residue replacements, identified a low-affinity site in fatty acid-binding site 6 (domain II). Surface plasmon resonance (SPR) showed these replacements affect the kinetics of the high-affinity binding site. Furthermore, small-angle X-ray scattering and SPR brace two somapacitan-binding sites on HSA.

show abstract

Section: Materials and Methodsmentioning

confidence: 99%

Identification of Binding Sites on Human Serum Albumin for Somapacitan, a Long-Acting Growth Hormone Derivative

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The percentage of secondary structure components for hGH in the bulk solution and the complex with polymers are listed in Table 2. The helical content of the reference crystal structure 38 is 54.3%. The results in Table 2 show that in the aqueous medium, the percentage of the protein α-helices (54.82%) is higher than the reference molecule, and it can be concluded that the water environment does not interfere with the hGH secondary conformation.…”

Section: Resultsmentioning

confidence: 99%

“…The starting structure of the human growth hormone for the MD simulations was taken from the Protein Data Bank (PDB ID: 1HGU). 38 Missing residues and atoms in the crystal structure were added using MODELLER software. 39 The study is aimed at linear polymers and copolymers of 30 units in length.…”

Section: Methodsmentioning

confidence: 99%

Insight into the Microcosm of the Human Growth Hormone and Its Interactions with Polymers and Copolymers: A Molecular Dynamics Perspective

et al. 2020

View full text Add to dashboard Cite

Therapeutic proteins nowadays have increasingly been applied for their considerable potential in treating a wide variety of diseases. The effectiveness and potency of native therapeutic proteins are limited by various factors (e.g., stability, blood circulation time, specificity). Over the past years, a great deal of effort has been devoted to developing safe and efficient protein delivery systems. Entrapment of protein into polymeric and copolymeric matrices is common among the different types of proteinbased drug formulation. However, despite the massive efforts toward developing therapeutic protein delivery in experimental studies and industrial applications, there is relatively little data on the influence of polymers and copolymers on therapeutic proteins at the atomic and molecular levels. Herein, molecular dynamics (MD) simulations are used to study the effects of biocompatible synthetic polymers including methoxy poly(ethylene glycol) (MPEG), poly(lactic acid) (PLA), and poly(lactic acid) copolymers (poly(lacticco-glycolic acid)) PLGA and MPEG-PLA(PELA)) on the structure and dynamics of the human growth hormone (hGH), and the results are compared with previous experimental findings. Our results indicate that the hGH conformation remains stable both in pure water and in the presence of polymers, and these results are in good agreement with previous experimental data. It is shown that the MPEG chains are self-assembled and folded into a semicrystalline structure; therefore, only a small portion of the protein interacts with the polymer. The other three polymers, however, interact well with the protein and partially cover its surface. Our findings suggest that the use of these polymers for protein encapsulation has the advantage of reducing protein aggregation and thus increasing drug serum half-life. Eventually, we anticipate that the research results will expand the current knowledge about encapsulation mechanisms and the molecular interactions between hGH and the polymers.

show abstract

“…Analysis of the crystallographic structures of receptorbound and free human growth hormone reveals that GH is an anti-parallel four-helix bundle protein containing two disulfide bridges, Cys53 -Cys165 and Cys182 -189 [3,24]. The two structures are closely similar, except for some short helices connecting the four major helical segments.…”

Section: Gh Isoformsmentioning

confidence: 99%

Growth hormone isoforms and segments/fragments: Molecular structure and laboratory measurement

Palo

Filippis

Gatti

et al. 2006

Clinica Chimica Acta

View full text Add to dashboard Cite

The Crystal Structure of Wild-Type Growth Hormone at 2.5 a Resolution

Cited by 56 publications

References 0 publications

Identification of Binding Sites on Human Serum Albumin for Somapacitan, a Long-Acting Growth Hormone Derivative

Identification of Binding Sites on Human Serum Albumin for Somapacitan, a Long-Acting Growth Hormone Derivative

Insight into the Microcosm of the Human Growth Hormone and Its Interactions with Polymers and Copolymers: A Molecular Dynamics Perspective

Growth hormone isoforms and segments/fragments: Molecular structure and laboratory measurement

Contact Info

Product

Resources

About