Molecular recognition between serine proteases and new bioactive microproteins with a knotted structure

Nguyen, Duy Linh; Heitz, Annie; Chiche, Laurent; Castro, Bertrand; Boigegrain, Rose-Anne; Favel, Anne; Ma, Che

doi:10.1016/0300-9084(90)90067-q

Cited by 121 publications

(88 citation statements)

References 13 publications

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“…The third bridge (Cys3-Cys20) was deduced indirectly via long-range connectivities between residues Cys20 and Ile4. The proposed disulfide pairings, Cys3-Cys20, Cys10-Cys24, and Cys19-Cys35, are fully compatible with the disulfide bond pattern found for a group of peptides collectively termed "knottins" (27). Secondary Structure.…”

Section: Sequential Assignment and Disulfide Pairingssupporting

confidence: 70%

Solution Structure of PAFP-S: A New Knottin-Type Antifungal Peptide from the Seeds of Phytolacca americana^,

et al. 2001

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The three-dimensional solution structure of PAFP-S, an antifungal peptide extracted from the seeds of Phytolacca americana, was determined using 1 H NMR spectroscopy. This cationic peptide contains 38 amino acid residues. Its structure was determined from 302 distance restraints and 36 dihedral restraints derived from NOEs and coupling constants. The peptide has six cysteines involved in three disulfide bonds. The previously unassigned parings have now been determined from NMR data. The solution structure of PAFP-S is presented as a set of 20 structures using ab initio dynamic simulated annealing, with an average RMS deviation of 1.68 Å for the backbone heavy atoms and 2.19 Å for all heavy atoms, respectively. For the well-defined triple-stranded -sheet involving residues 8-10, 23-27, and 32-36, the corresponding values were 0.39 and 1.25 Å. The global fold involves a cystine-knotted three-stranded antiparallel -sheet (residues 8-10, 23-27, 32-36), a flexible loop (residues 14-19), and four -reverse turns (residues 4-8, 11-14, 19-22, 28-32). This structure features all the characteristics of the knottin fold. It is the first structural model of an antifungal peptide that adopts a knottin-type structure. PAFP-S has an extended hydrophobic surface comprised of residues Tyr23, Phe25, Ile27, Tyr32, and Val34. The side chains of these residues are well-defined in the NMR structure. Several hydrophilic and positively charged residues (Arg9, Arg38, and Lys36) surround the hydrophobic surface, giving PAFP-S an amphiphilic character which would be the main structural basis of its biological function.

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Section: Sequential Assignment and Disulfide Pairingssupporting

confidence: 70%

Solution Structure of PAFP-S: A New Knottin-Type Antifungal Peptide from the Seeds of Phytolacca americana^,

et al. 2001

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“…The disulfides C2-C5 and C3-C6 superimpose very well in all inhibitor cystine knots including AVR9, and are thus most conserved. The C1-C4 bridge is only poorly superimposable in all proteins and seems to play a minor role in folding as has been determined for EETI-II [42].…”

Section: Discussionmentioning

confidence: 78%

The race‐specific elicitor AVR9 of the tomato pathogen Cladosporium fulvum: a cystine knot protein

Vervoort¹,

Hooven²,

Berg³

et al. 1997

FEBS Letters

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The secondary structure and global fold of the AVR9 elicitor protein of Cladosporium fulvum has been determined by 2D NMR and distance-geometry protocols. The protein consists of three anti-parallel strands forming a rigid region of P-sheet. On the basis of the NMR-derived parameters and distance geometry calculations, it is evident that the AVR9 protein is structurally very homologuous to carboxy peptidase inhibitor (CPI) of which the X-ray structure is known. The AVR9 protein reveals the presence of a cystine knot, which consists of a ring formed by two disulfide bridges and the interconnecting backbone through which the third disulfide bridge penetrates. This structural motif is found in several small proteins such as proteinase inhibitors, ion channel blockers and growth factors. The implications of the structural relationship between AVR9 and other biologically active proteins are discussed.

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“…Kikuchi et al (1986) found four examples of pseudolinked proteins among 18 structures examined. Other cases of pseudolinking also have been reported (Le Nguyen et al, 1990). For pseudolinking to occur after disulfide bond formation, as Figure 5 shows may happen, threading of the polypeptide chain through a preexisting loop would be required.…”

Section: Embedded Topologies-linkagesmentioning

confidence: 73%

“…No examples of topological knotting were found in this case-bycase search. To date all structures that were reported to be knotted have proven to be pseudolinked (Le Nguyen et al, 1990). Again, nontrivial topology of this type has not been detected in the sample of molecules surveyed.…”

Section: Embedded Topologies -Knottingmentioning

confidence: 95%

“…Because this rotation is a continuous deformation, apparent linkage of nondisjoint bonds is not topological in character. Nontopological loop interpenetrations of this type, called pseudolinks, are known to occur in proteins (Kinemage 1; Kikuchi et al, 1986;Le Nguyen et al, 1990). However, because pseudolinkage is not a topological condition, its consideration will be deferred to a later time.…”

Section: Embedded Topologies-linkagesmentioning

confidence: 99%

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Disulfide bonding patterns and protein topologies

Benham

Jafri

1993

Protein Science

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This paper examines the topological properties of protein disulfide bonding patterns. First, a description of these patterns in terms of partially directed graphs is developed. The topologically distinct disulfide bonding patterns available to a polypeptide chain containing n disulfide bonds are enumerated, and their symmetry and reducibility properties are examined. The theoretical probabilities are calculated that a randomly chosen pattern of n bonds will have any combination of symmetry and reducibility properties, given that all patterns have equal probability of being chosen. Next, the National Biomedical Research Foundation protein sequence and Brookhaven National Laboratories protein structure (PDB) databases are examined, and the occurrences of disulfide bonding patterns in them are determined. The frequencies of symmetric and/or reducible patterns are found to exceed theoretical predictions based on equiprobable pattern selection. Kauzmann's model, in which disulfide bonds form during random encounters as the chain assumes random coil conformations, finds that bonds are more likely to form with near neighbor cysteines than with remote cysteines. The observed frequencies of occurrence of disulfide patterns are found here to be virtually uncorrelated with the predictions of this alternative random bonding model. These results strongly suggest that disulfide bond pattern formation is not the result of random factors, but instead is a directed process.Finally, the PDB structure database is examined to determine the extrinsic topologies of polypeptides containing disulfide bonds. A complete survey of all structures in the database found no instances in which two loops formed by disulfide bonds within the same polypeptide chain are topologically linked. Similarly, no instances are found in which two loops present on different polypeptide chains in a structure are catenated. Further, no examples of topologically knotted loops occur. In contrast, pseudolinking has been found to be a relatively frequent event. These results show a complete avoidance of nontrivial topological entanglements that is unlikely to be the result of chance events. A hypothesis is presented to account for some of these observations. Keywords: covalent bond topology; entanglements; knots; protein structure Topology is the branch of mathematics that studies those properties of shape that remain invariant under continuous deformations. Topological properties naturally subdivide into two types -those that derive from the intrinsic structure of the object under study, and those that relate to how that structure is embedded in space. For example, a closed circle has a different intrinsic topological structure than a finite line segment. One can convert a circle into a line segment only by introducing a cut, which is a discontinuous deformation. As these two structures have different intrinsic topologies, one naturally might expect them also t o have different ranges of possible realizations in space. All embeddings of a finite linear s...

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Molecular recognition between serine proteases and new bioactive microproteins with a knotted structure

Cited by 121 publications

References 13 publications

Solution Structure of PAFP-S: A New Knottin-Type Antifungal Peptide from the Seeds of Phytolacca americana^,

Solution Structure of PAFP-S: A New Knottin-Type Antifungal Peptide from the Seeds of Phytolacca americana^,

The race‐specific elicitor AVR9 of the tomato pathogen Cladosporium fulvum: a cystine knot protein

Disulfide bonding patterns and protein topologies

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Molecular recognition between serine proteases and new bioactive microproteins with a knotted structure

Cited by 121 publications

References 13 publications

Solution Structure of PAFP-S: A New Knottin-Type Antifungal Peptide from the Seeds of Phytolacca americana,

Solution Structure of PAFP-S: A New Knottin-Type Antifungal Peptide from the Seeds of Phytolacca americana,

The race‐specific elicitor AVR9 of the tomato pathogen Cladosporium fulvum: a cystine knot protein

Disulfide bonding patterns and protein topologies

Contact Info

Product

Resources

About

Solution Structure of PAFP-S: A New Knottin-Type Antifungal Peptide from the Seeds of Phytolacca americana^,

Solution Structure of PAFP-S: A New Knottin-Type Antifungal Peptide from the Seeds of Phytolacca americana^,