3dSS: 3D structural superposition

Sumathi, K.; Ananthalakshmi, P.; Roshan, M. N. A. Md.; Sekar, K.

doi:10.1093/nar/gkl036

Cited by 118 publications

(78 citation statements)

References 25 publications

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“…Superposition and location of invariant water molecules were made using the program 3dss (21). Interfacial water molecules were located with the program Water Analysis Package (22).…”

Section: Methodsmentioning

confidence: 99%

Structural Basis of Neutralization of the Major Toxic Component from the Scorpion Centruroides noxius Hoffmann by a Human-derived Single-chain Antibody Fragment

Canul-Tec

Riaño-Umbarila

Rudino‐Pinera

et al. 2011

Journal of Biological Chemistry

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It has previously been reported that several single-chain antibody fragments of human origin (scFv) neutralize the effects of two different scorpion venoms through interactions with the primary toxins of Centruroides noxius Hoffmann (Cn2) and Centruroides suffusus suffusus (Css2). Here we present the crystal structure of the complex formed between one scFv (9004G) and the Cn2 toxin, determined in two crystal forms at 2.5 and 1.9 Å resolution. A 15-residue span of the toxin is recognized by the antibody through a cleft formed by residues from five of the complementarity-determining regions of the scFv. Analysis of the interface of the complex reveals three features. First, the epitope of toxin Cn2 overlaps with essential residues for the binding of ␤-toxins to its Na ؉ channel receptor site. Second, the putative recognition of Css2 involves mainly residues that are present in both Cn2 and Css2 toxins. Finally, the effect on the increase of affinity of previously reported key residues during the maturation process of different scFvs can be inferred from the structure. Taken together, these results provide the structural basis that explain the mechanism of the 9004G neutralizing activity and give insight into the process of directed evolution that gave rise to this family of neutralizing scFvs.The most harmful components of scorpion venoms are toxins that can selectively bind to voltage-gated ion channels and affect their modulation. A subgroup among these toxins, the long chain Na ϩ channel toxins, are formed by 60 -70-amino acid peptides, which adopt a highly packed core with a ␤␣␤␤-fold (1). These Na ϩ channel toxins have further been classified into two major classes (␣ and ␤) based on their effects in the gating mechanism of Na ϩ channels and their properties (2-4). The old world toxin II from Androctonus Australia Hector (AaHII) and the new world toxin II from Centruroides suffusus suffusus (Css2) 4 are considered to be the archetypes of ␣-and ␤-toxins active against mammals, respectively (3, 5).The buthid scorpion, C. suffusus suffusus, is one of the most poisonous to the rural human population in the Northwest of Mexico. The most noxious and abundant molecule found in the venom of this scorpion is Css2 (LD 50 of 0.7 g/20 g of mice of the strain CD1) (6). In addition, the Mexican scorpion Centruroides noxius Hoffmann produces toxin Cn2, one of the most abundant and noxious peptides against mammals (LD 50 of 0.25 g/20 g of mice of the strain CD1) (7). Sequence comparison shows that Cn2 presents a high similarity with other ␤-toxins from C. suffusus suffusus, such as Css2 and Css4 (around 90%, see below). Both toxins, Cn2 and Css2, are specific to Na ϩ channel subtype Na v 1.6 (6, 8).Due to the fact that scorpion stings are a considerable public health issue in a number of countries (9), efforts have been put forth to explore alternative technologies to generate more specific antibodies against the venom of scorpions harmful to humans (reviewed in Ref. 10). One of the most promising alternatives to classical...

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“…Superposition and location of invariant water molecules were made using the program 3dss (21). Interfacial water molecules were located with the program Water Analysis Package (22).…”

Section: Methodsmentioning

confidence: 99%

Structural Basis of Neutralization of the Major Toxic Component from the Scorpion Centruroides noxius Hoffmann by a Human-derived Single-chain Antibody Fragment

Canul-Tec

Riaño-Umbarila

Rudino‐Pinera

et al. 2011

Journal of Biological Chemistry

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“…Docking studies revealed that the "hydrophobic tail" at the amp-2 N-terminus has a key role in membrane interaction (Figure 6b) 49 , forming a hydrogen interaction between nitrogen (ND2) and oxygen, respectively, with a distance of 2.8 Å. The "hydrophobic tail" added into amp-2 also showed an interesting property since it probably involved a hydrogen bond formation between nitrogen (N7) of modification and oxygen head group (O14) in DPPE 18 with a distance of 2.8 Å (Table 3).…”

Section: Resultsmentioning

confidence: 99%

“…In the amp-2 interaction toward a Gram-positive membrane (Figure 7b) it was possible to identify the insertion into membrane core involving the "hydrophobic tail" (C 6 H 12 N). This insertion is probably firstly guided through hydrogen bond formation between nitrogen (N7) and oxygen head group of phospholipids DPPE 18 with a distance around 3.3 Å. Probably hydrophobic interactions inside the core might be formed with the insertion of the "hydrophobic tail", since the distance observed was less than 3.5 Å ( Table 4).…”

Section: Resultsmentioning

confidence: 99%

“…The amp-1 and amp-2 final models (i.e., geometry, stereochemistry, and energy distributions in the models, were evaluated using PROSA II to analyze packing and solvent exposure characteristics and PROCHECK for additional analysis of stereochemical quality [17]. In addition, RMSD was calculated by overlap of Cα traces and backbones onto the template structure through the program 3DSS [18]. The peptide structures were visualized and analyzed on Delano Scientific's PYMOL [19] http:// pymol.sourceforge.net/.…”

Section: Molecular Modelingmentioning

confidence: 99%

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The Use of MALDI-TOF-MS and In Silico Studies for Determination of Antimicrobial Peptides’ Affinity to Bacterial Cells

Mandal

Migliolo²,

Franco³

2012

J. Am. Soc. Mass Spectrom.

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Several methods have been proposed for determining the binding affinity of antimicrobial peptides (AMPs) to bacterial cells. Here the utilization of MALDI-TOF-MS was proposed as a reliable and efficient method for high throughput AMP screening. The major advantage of the technique consists of finding AMPs that are selective and specific to a wide range of Gramnegative and -positive bacteria, providing a simple reliable screening tool to determine the potential candidates for broad spectrum antimicrobial drugs. As a prototype, amp-1 and -2 were used, showing highest activity toward Gram-negative and -positive membranes respectively. In addition, in silico molecular docking studies with both peptides were carried out for the membranes. In silico results indicated that both peptides presented affinity for DPPG and DPPE phospholipids, constructed in order to emulate an in vivo membrane bilayer. As a result, amp-1 showed a higher complementary surface for Gram-negative while amp-2 showed higher affinity to Gram-positive membranes, corroborating MS analyses. In summary, results here obtained suggested that in vitro methodology using MALDI-TOF-MS in addition to theoretical studies may be able to improve AMP screening quality.

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“…However, one may find it interesting to note that the strands 2 and 3 are intact in all the time averaged structures. Further, superposition of the crystal and simulated structures performed using 3dss [34] revealed that the 2 and 3 -strands are preserved in their respective orientations (data not shown). The time averaged native and mutant structures show a decrease in content of secondary structural elements.…”

Section: Assessment Of Secondary Structuresmentioning

confidence: 98%

Influence of Disulfide Bonds on the Conformation of the Antifungal Protein from Oliver

Jayanthi¹,

Kangueane²,

Prakash³

et al. 2009

TOSBJ

Self Cite

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Abstract:The three-dimensional structure of a cysteine rich antifungal protein EAFP2 is found to be compact and extremely stable. The rigid nature of the protein is attributed to the presence of five disulfide bonds. However, the effect of individual disulfide bonds on the conformation has not been characterized. Thus, Molecular Dynamics (MD) simulations are used to explicate the influence of disulfide bonds on the conformation. In the present study, the cysteine residues in the native structure are mutated to alanine and the structural characteristics and conformational dynamics of the native and mutant structures are analyzed to better understand the effect of disulfide bonds on the tertiary structure. The simulated native and single mutant structures are found to posses similar conformations, indicating that loss of disulfide bond did not affect the tertiary structure conformation greatly. However, in the single mutant (C7A) structure, the N and C-terminal segments are found to be different. It is also interesting to note that the loss of disulfide bond between Cys35 and Cys39 actually resulted in a more compact structure.

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3dSS: 3D structural superposition

Cited by 118 publications

References 25 publications

Structural Basis of Neutralization of the Major Toxic Component from the Scorpion Centruroides noxius Hoffmann by a Human-derived Single-chain Antibody Fragment

Structural Basis of Neutralization of the Major Toxic Component from the Scorpion Centruroides noxius Hoffmann by a Human-derived Single-chain Antibody Fragment

The Use of MALDI-TOF-MS and In Silico Studies for Determination of Antimicrobial Peptides’ Affinity to Bacterial Cells

Influence of Disulfide Bonds on the Conformation of the Antifungal Protein from Oliver

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