Conformational Studies of Oligosaccharides and Glycopeptides:  Complementarity of NMR, X-ray Crystallography, and Molecular Modelling

Wormald, Mark R.; Petrescu, Andrei‐Jose; Pao, Ya-Lan; Glithero, Ann; Elliott, Tim; Dwek, Raymond A.

doi:10.1021/cr990368i

Cited by 399 publications

(357 citation statements)

References 74 publications

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“…In each case, the N-terminal and C-terminal domains were then added before a final round of energy minimization. N-Linked and O-linked glycan structures, chosen on the basis of the sequencing results, were generated using the data base of glycosidic linkage conformations (42) and in vacuo energy minimization to relieve unfavorable steric interactions. For the N-linked glycans, Asn-GlcNAc linkage conformations were based on the observed range of crystallographic values (43), the torsion angles around the Asn C␣-C␤ and C␤-C␥ bonds then being adjusted to eliminate unfavorable steric interactions between the glycans and the protein surface.…”

Section: Molecular Modelingmentioning

confidence: 99%

The Hemopexin and O-Glycosylated Domains Tune Gelatinase B/MMP-9 Bioavailability via Inhibition and Binding to Cargo Receptors

Steen

Aelst

Hvidberg

et al. 2006

Journal of Biological Chemistry

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169

206

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Gelatinase B/matrix metalloproteinase-9 (MMP-9), a key regulator and effector of immunity, contains a C-terminal hemopexin domain preceded by a unique linker sequence of ϳ64 amino acid residues. This linker sequence is demonstrated to be an extensively O-glycosylated (OG) domain with a compact three-dimensional structure. The OG and hemopexin domains have no influence on the cleavage efficiency of MMP-9 substrates. In contrast, the hemopexin domain contains a binding site for the cargo receptor low density lipoprotein receptor-related protein-1 (LRP-1). Furthermore, megalin/ LRP-2 is identified as a new functional receptor for the hemopexin domain of MMP-9, able to mediate the endocytosis and catabolism of the enzyme. The OG domain is required to correctly orient the hemopexin domain for inhibition by TIMP-1 and internalization by LRP-1 and megalin. Therefore, the OG and hemopexin domains down-regulate the bioavailability of active MMP-9 and the interactions with the cargo receptors are proposed to be the original function of hemopexin domains in MMPs.

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Section: Molecular Modelingmentioning

confidence: 99%

The Hemopexin and O-Glycosylated Domains Tune Gelatinase B/MMP-9 Bioavailability via Inhibition and Binding to Cargo Receptors

Steen

Aelst

Hvidberg

et al. 2006

Journal of Biological Chemistry

Self Cite

169

206

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“…Furthermore, NMR has been widely applied in clinical research, called magnetic resonance imaging (MRI), to help physicians diagnose potential disease regions in soft tissues, such as human brains (91). Furthermore, other than proteins, NMR may be also applied to study the dynamics of ribonucleic acid (RNA) (92), as well as the structure and conformational changes of carbohydrates (93).…”

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confidence: 99%

Structural Basis for Interactions of thePhytophthora sojaeRxLR Effector Avh5 with Phosphatidylinositol 3-Phosphate and for Host Cell Entry

Sun¹,

Kale²,

Azurmendi³

et al. 2013

MPMI

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Oomycetes, such as Phytophthora sojae, are plant pathogens that employ protein effectors that enter host cells to facilitate infection. Plants may overcome infection by recognizing pathogen effectors via intracellular receptors (R proteins) that form part of their defense system. Entry of some effector proteins into plant cells is mediated by conserved RxLR motifs in the effectors and phosphoinositides (PIPs) resident in the host plasma membrane such as phosphatidylinositol 3-phosphate (PtdIns(3)P). Recent reports differ regarding the regions on RxLR effector proteins involved in PIP recognition. To clarify these differences, I have structurally and functionally characterized the P. sojae effector, avirulence homolog-5 (Avh5).

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“…The glycose linkages are influenced by the solvent (26), thereby modifying their biological specificity. In some circumstances, these linkages may be stiffened by solventmediated hydrogen bonding, whereas in other linkages they are found to be very flexible (27,28). The (134) linkage found in lactose also is present in many carbohydrate structures, including plant cell walls and insect skeletons and is a common motif in N-linked glucoproteins.…”

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confidence: 99%

Solute-induced retardation of water dynamics probed directly by terahertz spectroscopy

Heugen

Schwaab

Bründermann

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

383

338

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Hydrogen bond rearrangement in water occurs on the picosecond time scale, so relevant experiments must access these times. Here, we show that terahertz spectroscopy can directly investigate hydration layers. By a precise measurement of absorption coefficients between 2.3 THz and 2.9 THz we could determine the size and the characteristics of the hydration shell. The hydration layer around a carbohydrate (lactose) is determined to extend to 5.13 ؎ 0.24 Å from the surface corresponding to Ϸ123 water molecules beyond the first solvation shell. Accompanying molecular modeling calculations support this result and provide a microscopic visualization. Terahertz spectroscopy is shown to probe the collective modes in the water network. The observed increase of the terahertz absorption of the water in the hydration layer is explained in terms of coherent oscillations of the hydration water and solute. Simulations also reveal a slowing down of the hydrogen bond rearrangement dynamics for water molecules near lactose, which occur on the picosecond time scale. The present study demonstrates that terahertz spectroscopy is a sensitive tool to detect solute-induced changes in the water network.hydration water dynamics ͉ molecular dynamics simulations of biomolecules ͉ solvated lactose T he many unusual properties of water combined with its importance as the solvent of life account for its continued study by numerous researchers. Indeed, the properties of water are essential in the behavior of all biological systems. For example, water plays a central role in the folding and function of proteins, and the function of carbohydrates. The dynamics of water surrounding a solute is of fundamental importance in a wide range of processes in solution. In particular, the properties of water molecules near the surface of a biomolecule have been the subject of numerous and sometimes controversial experimental and theoretical studies (1-5). The characteristics and role of this ''biological'' water, with properties that differ considerably from those of bulk water, are still not fully understood (6).The importance of the hydration layer or the biological water is obvious in specific protein processes, such as opening and closing of channels, the kinetics of which has been found to be coupled with the solvent fluctuations (1). Important questions that remain so far unanswered include the following: How does solvation water differ from bulk water, and how large is the solvation layer that can be attributed to solvent water? Simulations suggest the existence of rather rigid water structures around proteins (5) and carbohydrates (7), but experimental studies that characterize the hydration layer are limited. Hydrogen bond rearrangements in water occur on the picosecond time scale (8), so that a detailed understanding of the relevant processes at a molecular level requires experimental techniques that are able to probe the hydration layers on this time scale. However, experimental investigations of fast dynamics of hydration water still remain a ch...

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Conformational Studies of Oligosaccharides and Glycopeptides: Complementarity of NMR, X-ray Crystallography, and Molecular Modelling

Cited by 399 publications

References 74 publications

The Hemopexin and O-Glycosylated Domains Tune Gelatinase B/MMP-9 Bioavailability via Inhibition and Binding to Cargo Receptors

The Hemopexin and O-Glycosylated Domains Tune Gelatinase B/MMP-9 Bioavailability via Inhibition and Binding to Cargo Receptors

Structural Basis for Interactions of thePhytophthora sojaeRxLR Effector Avh5 with Phosphatidylinositol 3-Phosphate and for Host Cell Entry

Solute-induced retardation of water dynamics probed directly by terahertz spectroscopy

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