The role of water in sequence-independent ligand binding by an oligopeptide transporter protein

Tame, J.R.H.; Sleigh, S.H.; Wilkinson, Anthony J.; Ladbury, John E.

doi:10.1038/nsb1296-998

Cited by 135 publications

(122 citation statements)

References 21 publications

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“…However, one of the water molecules must be displaced to permit binding of the larger arginine ligand (23). In contrast, OppA provides an example of the use of solvent in decreasing ligand binding specificity through the accommodation of multiple substrates with different peptide side chains in voluminous hydrated cavities from which water molecules are readily gained or lost (24). In the structure of ␣-chymotrypsin complexed with a turkey ovomucoid inhibitor, it was demonstrated that a water molecule, also present in the apo structure, mediated an ionic interaction that was critical for inhibitor binding specificity (25).…”

Section: Fig 2 Structure Of the Purr-guanine-purf Operator Complexmentioning

confidence: 99%

The X-ray Structure of the PurR-Guanine-purF Operator Complex Reveals the Contributions of Complementary Electrostatic Surfaces and a Water-mediated Hydrogen Bond to Corepressor Specificity and Binding Affinity

Schumacher¹,

Glasfeld²,

Zalkin³

et al. 1997

Journal of Biological Chemistry

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The purine repressor, PurR, is the master regulatory protein of de novo purine nucleotide biosynthesis in Escherichia coli. This dimeric transcription factor is activated to bind to cognate DNA operator sites by initially binding either of its physiologically relevant, high affinity corepressors, hypoxanthine (K d ‫؍‬ 9.3 M) or guanine (K d ‫؍‬ 1.5 M). Here, we report the 2.5-Å crystal structure of the PurR-guanine-purF operator ternary complex and complete the atomic description of 6-oxopurine-induced repression by PurR. As anticipated, the structure of the PurR-guanine-purF operator complex is isomorphous to the PurR-hypoxanthine-purF operator complex, and their protein-DNA and protein-corepressor interactions are nearly identical. The former finding confirms the use of an identical allosteric DNA-binding mechanism whereby corepressor binding 40 Å from the DNA-binding domain juxtaposes the hinge regions of each monomer, thus favoring the formation and insertion of the critical minor groove-binding hinge helices. Strikingly, the higher binding affinity of guanine for PurR and the ability of PurR to discriminate against 2-oxopurines do not result from direct protein-ligand interactions, but rather from a water-mediated contact with the exocyclic N-2 of guanine, which dictates the presence of a donor group on the corepressor, and the better electrostatic complementarity of the guanine base and the corepressor-binding pocket.

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Section: Fig 2 Structure Of the Purr-guanine-purf Operator Complexmentioning

confidence: 99%

The X-ray Structure of the PurR-Guanine-purF Operator Complex Reveals the Contributions of Complementary Electrostatic Surfaces and a Water-mediated Hydrogen Bond to Corepressor Specificity and Binding Affinity

Schumacher¹,

Glasfeld²,

Zalkin³

et al. 1997

Journal of Biological Chemistry

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“…DppA mediates the chemotactic response of E. coli toward dipeptides, but OppA has no such function. OppA is the most thoroughly characterized PBP (31,32). The protein binds peptide ligands with affinities spanning at least three orders of magnitude (K d ϭ 10 M-10 nM).…”

Section: Figmentioning

confidence: 99%

“…OppA is the most unselective PBP, being able to bind short peptides with relatively little side-chain preference (31,32). In contrast, most solute-binding proteins are highly selective and show dissociation constants of around 1-0.1 M for their ligands.…”

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confidence: 99%

Crystal Structures of the Liganded and Unliganded Nickel-binding Protein NikA from Escherichia coli

Heddle

Scott

Unzai

et al. 2003

Journal of Biological Chemistry

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114

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Bacteria have evolved a number of tightly controlled import and export systems to maintain intracellular levels of the essential but potentially toxic metal nickel. Nickel homeostasis systems include the dedicated nickel uptake system nik found in Escherichia coli, a member of the ABC family of transporters, that involves a periplasmic nickel-binding protein, NikA. This is the initial nickel receptor and mediator of the chemotactic response away from nickel. We have solved the crystal structure of NikA protein in the presence and absence of nickel, showing that it behaves as a "classical" periplasmic binding protein. In contrast to other binding proteins, however, the ligand remains accessible to the solvent and is not completely enclosed. No direct bonds are formed between the metal cation and the protein. The nickel binding site is apolar, quite unlike any previously characterized protein nickel binding site. Despite relatively weak binding, NikA is specific for nickel. Using isothermal titration calorimetry, the dissociation constant for nickel was found to be ϳ10 M and that for cobalt was approximately 20 times higher.

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“…In the resolution range of 0.9 -1.2 A , , most structures contain B 350 residues and only one structure with 269 residues diffracts to 0.78 A , resolution (24).…”

mentioning

confidence: 99%

A New Functional Domain of Guanine Nucleotide Dissociation Inhibitor (α‐GDI) Involved in Rab Recycling

Luan

Heine

Zeng

et al. 2000

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Guanine nucleotide dissociation inhibitor (GDI) is a 55-kDa protein that functions in vesicular membrane transport to recycle Rab GTPases. We have now determined the crystal structure of bovine a-GDI at ultra-high resolution (1.04 A , ). Refinement at this resolution highlighted a region with high mobility of its main-chain residues. This corresponded to a surface loop in the primarily a-helical domain II at the base of a-GDI containing the previously uncharacterized sequence-conserved region (SCR) 3A. Site-directed mutagenesis showed that this mobile loop plays a crucial role in binding of GDI to membranes and extraction of membrane-bound Rab. This domain, referred to as the mobile effector loop, in combination with Rab-binding residues found in the multi-sheet domain I at the apex of a-GDI may provide flexibility for recycling of diverse Rab GTPases. We propose that conserved residues in domains I and II synergize to form the functional face of GDI, and that domain II mediates a critical step in Rab recycling during vesicle fusion.

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The role of water in sequence-independent ligand binding by an oligopeptide transporter protein

Cited by 135 publications

References 21 publications

The X-ray Structure of the PurR-Guanine-purF Operator Complex Reveals the Contributions of Complementary Electrostatic Surfaces and a Water-mediated Hydrogen Bond to Corepressor Specificity and Binding Affinity

The X-ray Structure of the PurR-Guanine-purF Operator Complex Reveals the Contributions of Complementary Electrostatic Surfaces and a Water-mediated Hydrogen Bond to Corepressor Specificity and Binding Affinity

Crystal Structures of the Liganded and Unliganded Nickel-binding Protein NikA from Escherichia coli

A New Functional Domain of Guanine Nucleotide Dissociation Inhibitor (α‐GDI) Involved in Rab Recycling

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