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PubMed1987

DNA sequence dependence of closely opposed cyclobutyl pyrimidine dimers induced by UV radiation.

Treatment of UV-irradiated DNAs with Micrococcus luteus pyrimidine dimer-DNA glycosylase results in the formation of double-strand breaks due to cleavage at closely opposed pyrimidine dimers. To determine if the induction of closely opposed dimers is significantly affected by DNA nucleotide sequence, end-labeled DNA fragments of known nucleotide sequence were UV irradiated, incubated with pyrimidine dimer-DNA glycosylase, and analyzed by electrophoresis through nondenaturing polyacrylamide gels. Distinct bands of increased electrophoretic mobility were observed, indicating that bifilar cleavage had occurred with greater probability at specific sites in each DNA sequence. In vitro enzymatic photoreactivation of dimers prior to treatment with pyrimidine dimer-DNA glycosylase prevented the appearance of bands. DNA sequence analysis revealed the presence of closely opposed runs of pyrimidines at sites of more frequent bifilar cleavage. Our results indicate that the induction of closely opposed dimers occurs with greater probability at specific sites in DNA sequences and that such sites are characterized by the presence of closely opposed pyrimidine runs.

Bacterial Proteins↗
PubMed1988

Ultraviolet radiation-induced lethality and repair of pyrimidine dimers in fish embryos.

Pimephales promelas (fathead minnow) embryos were used to show a correlation between induction of pyrimidine dimers in DNA and embryo death. Embryo killing was measured by a lack of heart-beat and blood circulation at 48 h post-ultraviolet radiation (UVR). When the embryos were exposed to various doses of UVR from a FS-40 sunlamp followed by exposure to photoreactivating light (PRL) (320-400 nm), the number of pyrimidine dimers decreased significantly. The photorepair of dimers was accompanied by a substantial increase in embryo survival. When embryo killing was examined as a function of the number of dimers present, dimers were identified as a major lesion involved in UVR-induced killing in these fish embryos. This in vivo study on photoreactivation treatment of fish embryos shows a direct association between UVR-induced pyrimidine dimers and embryo killing. In addition, when embryos were held in the dark for 9 h after UVR, 50% of the dimers were removed by excision repair.

Animals↗
PubMed1982

Loss of thymine dimers from mammalian cell DNA. The kinetics for antibody-binding sites are not the same as that for T4 endonuclease V sites.

Antiserum specific for thymine-containing dimers was used to assay DNA isolated from ultraviolet-irradiated cells following different repair periods. A 50% loss in antibody-binding sites was evident 1 h post-irradiation, and within 4 h 80% of the sites were removed. This result contrasts with data obtained with dimer-specific T4 endonuclease V and does not appear to be due to masking of the dimers by repair enzymes. T4 endonuclease V treatment of ultraviolet-irradiated DNA at 0 degree C resulted in conversion of the thymine dimers to apyrimidinic sites. This did not result in loss of antigenicity in either PM2 or CHO cell DNA. Likewise, treatment of ultraviolet-irradiated CHO cell DNA with T4 endonuclease at 37 degrees C did not change its antigenicity. These results suggest that aglycosylation of the dimers is not responsible for their inability to bind dimer-specific antibody 2-4 h post-irradiation. The possibility that T4 endonuclease V and the antiserum have different specificities for different dimers is discussed.

Animals↗
PubMed1990

Is the induction of pyrimidine cyclobutane dimers relevant for the high cytotoxic effect of 7-methylpyrido[3,4-c]psoralen plus UV-A?

Recently, it was shown that the photoactivation of 7-methylpyrido[3,4-c]psoralen (MPP), a highly phototoxic monofunctional compound, as well as leading to the direct cycloaddition of the molecule to pyrimidine bases, also induces the dimerization of adjacent pyrimidines in DNA in vitro (Moysan et al., 1988). For other psoralens, e.g., 8-methoxypsoralen (8-MOP), such a formation of pyrimidine dimers does not occur (Costalat et al., 1989). The relatively low number of pyrimidine dimers which one can estimate from such in vitro results to be formed in vivo in cell DNA after highly lethal MPP photosensitization does not indicate that these dimers have important direct biological consequences. They could, however, interact with MPP adducts and eventually greatly potentiate their action. In order to test this hypothesis, experiments were designed to mimic the photosensitization by MPP. CV-1 TC-7 cells were irradiated at 254 nm, to produce pyrimidine dimers, and subsequently treated with 8-MOP or angelicin plus 365-nm light, to produce psoralen adducts. The clonogenicity of these cells was compared to that of cells damaged only by irradiation at 254 nm or by psoralens plus 365-nm light. It was observed that, for the same amount of induced adducts, the lethal effect of photosensitization by MPP remains much higher than that of photosensitization by 8-MOP coupled to a large excess of pyrimidine dimers induced with 254-nm light. In fact, with both 8-MOP and angelicin, close to additive effects were observed between pyrimidine dimers and psoralen adducts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Disulfide-linked dimers of human adrenaline synthesizing enzyme PNMT are catalytically active.

The crystal structure of human phenylethanolamine N-methyltransferase (hPNMT) reveals a disulfide-linked dimer, despite the presence of reducing agent in the crystallisation conditions. By removing the reducing agent, hPNMT crystals grow more rapidly and at lower protein concentrations. However, it was unclear whether the disulfide bonds are only present in the crystal form or whether these affect enzyme activity. The solution oligomeric state of hPNMT was investigated using biochemical techniques and activity assays. We found that in the absence of reducing agent, hPNMT forms dimers in solution. Furthermore, the solution dimer of hPNMT incorporates disulfide bonds, since this form is sensitive to reducing agent. The C48A and C139A mutants of hPNMT, which are incapable of forming the disulfide bond observed in the crystal structure, have a decreased propensity to form dimer in solution. Those dimers that do form are also sensitive to reducing agent. Further, the C48A/C139A double mutant shows only monomeric behaviour. Both dimeric and monomeric hPNMT, as well as mutants have wildtype enzyme activity. These results show that a variety of disulfides, including those observed in the crystal structure, can form in solution. In addition, disulfide-linked dimers are as active as the monomeric enzyme indicating that the crystal structure of the protein is a valid target for inhibitor design.

Binding Sites↗
PubMed2005

The N-terminal octapeptide acts as a dimerization inhibitor of SARS coronavirus 3C-like proteinase.

The 3C-like proteinase of severe acute respiratory syndrome (SARS) coronavirus has been proposed to be a key target for structural-based drug design against SARS. Accurate determination of the dimer dissociation constant and the role of the N-finger (residues 1-7) will provide more insights into the enzyme catalytic mechanism of SARS 3CL proteinase. The dimer dissociation constant of the wild-type protein was determined to be 14.0microM by analytical ultracentrifugation method. The N-finger fragment of the enzyme plays an important role in enzyme dimerization as shown in the crystal structure. Key residues in the N-finger have been studied by site-directed mutagenesis, enzyme assay, and analytical ultracentrifugation. A single mutation of M6A was found to be critical to maintain the dimer structure of the enzyme. The N-terminal octapeptide N8 and its mutants were also synthesized and tested for their potency as dimerization inhibitors. Peptide cleavage assay confirms that peptide N8 is a dimerization inhibitor with a K(i) of 2.20mM. The comparison of the inhibitory activities of N8 and its mutants indicates that the hydrophobic interaction of Met-6 and the electrostatic interaction of Arg-4 contribute most for inhibitor binding. This study describes the first example of inhibitors targeting the dimeric interface of SARS 3CL proteinase, providing a novel strategy for drug design against SARS and other coronaviruses.

Binding Sites↗
PubMed2005

Thiocolchicine dimers: a novel class of topoisomerase-I inhibitors.

During a cellular screening of thiocolchicine analogs, thiocolchicine dimers resulted particularly active in cisplatin-resistant A2780-CIS cells. In order to discover by which mechanism(s) thiocolchicine dimers overcame cisplatin resistance, p53, p21waf1 and MLH1 were assessed by Western blot. Results pointed out that, when combined with cisplatin, dimers increased the amount of all the three proteins with respect to the levels obtained by single drug exposure, thereby suggesting an interference in the process of repair of the cisplatin-induced DNA lesions. Moreover, in isolated nuclei drugs were able to produce DNA breaks, as demonstrated by Comet assay, thereby proving that the compounds were able to target cell nucleus independently from microtubules. Since Topo-I (topoisomerase I) is directly involved in the DNA repair and such activity is overexpressed in cisplatin-resistant cells, Topo-I was investigated as a potential target. Using DNA relaxation assay, thiocolchicine dimers inhibited Topo-I, a property not shared by thiocolchicine. At variance with camptothecin, dimers did not produce cleavable complexes, thereby indicating that Topo-I inhibition occurs upstream of the religation step. To assess the mechanism of inhibition, an electrophoretic mobility shift assay between DNA and Topo-I was performed and revealed that thiocolchicine dimers specifically interfere with binding of Topo-I to DNA. The interference is specific since the same compounds did not modulate DNase activity and did not act as intercalating agents in the DNA unwinding assay. Finally, behaviour of dimers as spindle poisons was investigated and no relevant changes with respect to thiocolchicine in terms of interaction with microtubules were found.

Cell Line↗
PubMed2003

Hypotension with intravenous immunoglobulin therapy: importance of pH and dimer formation.

Therapy with intravenous immunoglobulin preparations has been used effectively in a wide range of conditions. Although generally well tolerated, intravenous immunoglobulin preparations may be associated with transient hypotension in some patients. This study examined the role of different immunoglobulin G fractions in the development of intravenous immunoglobulin-induced hypotension in an anaesthetized rat model and assessed the effects of a new liquid immunoglobulin prepared at a low pH on both the formation of immunoglobulin G dimers and the development of hypotension. The effects of this new preparation in an experimental autoimmune encephalomyelitis model were also evaluated. Results from the haemodynamic studies indicated that immunoglobulin G dimers in polyclonal immunoglobulin G are responsible for the hypotensive events associated with some immunoglobulin preparations. They also showed that adjustment to an acidic pH results in the rapid dissociation of immunoglobulin G dimers and prevents the development of hypotension. Additional experiments demonstrated that only immunoglobulin G dimers with a functional Fc fragment can bind to Fcgamma receptors on macrophages to induce the release of blood pressure-lowering mediators. Moreover, essentially monomeric Fc fragments can block the blood pressure-lowering effects of immunoglobulin G dimers. Preparation of a new liquid intravenous immunoglobulin with the pH adjusted to 4.3 prevents the formation of immunoglobulin G dimers even over long-term storage and does not significantly affect blood pressure in a rat model. This preparation is as effective as other intravenous immunoglobulin preparations in ameliorating symptoms of experimental autoimmune encephalomyelitis. These results, like those from previous studies, indicate that preparation of intravenous immunoglobulin at a low pH substantially reduces immunoglobulin G dimerization; this effect significantly decreases the potential for intravenous immunoglobulin to induce hypotension without reducing its clinically relevant biological activity.

Animals↗
PubMed2005

Synthesis, DNA-binding affinities, and binding mode of berberine dimers.

Six novel berberine dimers (3a-f) were synthesized in 37-84% yield from the reaction of berberrubine (2) with dihaloalkanes of varying lengths from two to seven carbons. Their interactions with calf thymus (CT) DNA and three double helical oligodeoxynucleotides, d(AAGAATTCTT)2, d(AAGCATGCTT)2, and d(TAAGAATTCTTA)2, were investigated by means of fluorometric titration and ethidium bromide (EB) displacement experiments. Compared with the monomeric parent berberine (1), these dimers' DNA-binding affinities increased up to approximately 100-fold, suggesting a cooperative interaction of the two berberine subunits in the molecules. Furthermore, these dimers linked by different spacers show a prominent structure-activity relationship when bound with oligodeoxynucleotides. The relative binding affinities are in the order of 3b>3a>3c>3d>3e>3f with d(AAGAATTCTT)2 and d(TAAGAATTCTTA)2, and 3b>3c>3a>3d>3e>3f with d(AAGCATGCTT)2. Dimer 3b, linked with a propyl chain, exhibits the highest binding affinity. This suggests that a propyl chain may be the most suitable spacer to bridge the two berberine units for DNA binding. Spectrophotometric titration and competitive EB displacement of berberine (1) and dimer 3b indicate that both berberine and its dimers form intercalating complexes with duplex DNA. A larger redshift, a stronger hypochromic effect, and a much higher EB displacement ratio, observed in 3b, indicate that the dimer is in more intimate contact with DNA than berberine. In addition, no obvious binding of canadine (4), a hydrogenated product of berberine, with CT DNA was observed, suggesting critical roles of the quaternary ammonium cation and planar structure in the DNA-binding of berberine.

Base Sequence↗
PubMed2006

Engineering a novel, stable dimeric streptavidin with lower isoelectric point.

We have engineered a soluble, stable two-chain dimeric streptavidin (TCD) in Escherchia coli. Examination of the three-dimensional structure of streptavidin aided by empirical binding free-energy calculations helped us to select mutations at subunit interfaces that dissociate the native tetramer and stabilize the desired dimer. We chose positions W120, L124, V125 and H127 and mutated them to 120D/124D/125D/127D (TCD-1); 120D/124N/125S/127D (TCD-2); and 120D/124D/125S/127D (TCD-3). The H127D mutation creates electrostatic repulsion that disrupts the dimer-dimer interface, but leaves it very hydrophobic. Therefore, W120, L124 and V125 were mutated to hydrophilic residues to increase dimer solubility. Among the three candidates, TCD-2 gave the best result: a stable, active dimer with K(d) for biotin of approximately 1x10(-7)M after purification by gel-filtration chromatography. The experimental results confirm the possibility of rational engineering of low-pI dimeric streptavidins. Reduced-size streptavidin mutants with a net negative charge may be more suitable than antibodies or wild-type streptavidin for the targeting step in radioimmunotherapy because they should clear faster from the bloodstream and the kidney.

Bacterial Proteins↗
PubMed2004

Solution structure of the dimeric SAM domain of MAPKKK Ste11 and its interactions with the adaptor protein Ste50 from the budding yeast: implications for Ste11 activation and signal transmission through the Ste50-Ste11 complex.

Ste11, a homologue of mammalian MAPKKKs, together with its binding partner Ste50 works in a number of MAPK signaling pathways of Saccharomyces cerevisiae. Ste11/Ste50 binding is mediated by their sterile alpha motifs or SAM domains, of which homologues are also found in many other intracellular signaling and regulatory proteins. Here, we present the solution structure of the SAM domain or residues D37-R104 of Ste11 and its interactions with the cognate SAM domain-containing region of Ste50, residues M27-Q131. NMR pulse-field-gradient (PFG) and rotational correlation time measurements (tauc) establish that the Ste11 SAM domain exists predominantly as a symmetric dimer in solution. The solution structure of the dimeric Ste11 SAM domain consists of five well-defined helices per monomer packed into a compact globular structure. The dimeric structure of the SAM domain is maintained by a novel dimer interface involving interactions between a number of hydrophobic residues situated on helix 4 and at the beginning of the C-terminal long helix (helix 5). The dimer structure may also be stabilized by potential salt bridge interactions across the interface. NMR H/2H exchange experiments showed that binding of the Ste50 SAM to the Ste11 SAM very likely involves the positively charged extreme C-terminal region as well as exposed hydrophobic patches of the dimeric Ste11 SAM domain. The dimeric structure of the Ste11 SAM and its interactions with the Ste50 SAM may have important roles in the regulation and activation of the Ste11 kinase and signal transmission and amplifications through the Ste50-Ste11 complex.

Amino Acid Sequence↗
PubMed2005

The crystal structure of the C-terminal fragment of yeast Hsp40 Ydj1 reveals novel dimerization motif for Hsp40.

The molecular chaperone Hsp40 functions as a dimer. The dimer formation is critical for Hsp40 molecular chaperone activity to facilitate Hsp70 to refold non-native polypeptides. We have determined the crystal structure of the C-terminal fragment of yeast Hsp40 Ydj1 that is responsible for Ydj1 dimerization by MAD method. The C-terminal fragment of Ydj1 comprises of the domain III of Ydj1 and the Ydj1 C-terminal dimerization motif. The crystal structure indicates that the dimerization motif of type I Hsp40 Ydj1 differs significantly from that of yeast type II Hsp40. The C terminus of type I Hsp40 Ydj1 from one monomer forms beta-strands with the domain III from the other monomer in the homo-dimer. The L372 from Ydj1 C terminus inserts its side-chain into a hydrophobic pocket on domain III. The modeled full-length Ydj1 dimer structure reveals that a large cleft is formed between the two monomers. The domain IIs of Ydj1 monomers that contain the zinc-finger motifs points directly against each other.

Amino Acid Motifs↗
PubMed2005

Mariner Mos1 transposase dimerizes prior to ITR binding.

The mariner Mos1 synaptic complex consists of a tetramer of transposase molecules that bring together the two ends of the element. Such an assembly requires at least two kinds of protein-protein interfaces. The first is involved in "cis" dimerization, and consists of transposase molecules bound side-by-side on a single DNA molecule. The second, which is involved in "trans" dimerization, consists of transposase molecules bound to two different DNA molecules. Here, we used biochemical and genetic methods to enhance the definition of the regions involved in cis and trans-dimerization in the mariner Mos1 transposase. The cis and trans-dimerization interfaces were both found within the first 143 amino acid residues of the protein. The cis-dimerization activity was mainly contained in amino acids 1-20. The region spanning from amino acid residues 116-143, and containing the WVPHEL motif, was involved in the cis- to trans-shift as well as in trans-dimerization stabilization. Although the transposase exists mainly as a monomer in solution, we provide evidence that the transposase cis-dimer is the active species in inverted terminal repeat (ITR) binding. We also observed that the catalytic domain of the mariner Mos1 transposase modulates efficient transposase-transposase interactions in the absence of the transposon ends.

Amino Acid Motifs↗
PubMed2005

The response regulator OmpR oligomerizes via beta-sheets to form head-to-head dimers.

In Escherichia coli, the EnvZ/OmpR two-component regulatory system regulates expression of the porin genes ompF and ompC in response to changes in osmolarity. It has recently become apparent that OmpR functions as a global regulator, by regulating the expression of many genes in addition to the porin genes. OmpR consists of two domains; phosphorylation of the N-terminal receiver domain increases DNA binding affinity of the C-terminal domain and vice versa. Many response regulators including PhoB and FixJ dimerize upon phosphorylation. Here, we demonstrate that OmpR dimerization is stimulated by phosphorylation or by DNA binding. The dimerization interface revealed here was unanticipated and had previously not been predicted. Using the accepted head-to-tail tandem-binding model as a guide, we set out to examine the intermolecular interactions between OmpR dimers bound to DNA by protein-protein cross-linking methods. Surprisingly, amino acid positions that we expected to form cross-linked dimers did not. Conversely, positions predicted not to form dimers did. Because of these results, we designed a series of 23 cysteine-substituted OmpR mutants that were used to investigate dimer interfaces formed via the beta-sheet region. This four-stranded beta-sheet is a unique feature of the OmpR group of winged helix-turn-helix proteins. Many of the cysteine-substituted mutants are dominant to wild-type OmpR, are phosphorylated by acetyl phosphate as well as the cognate kinase EnvZ, and the cross-linked proteins are capable of binding to DNA. Our results are consistent with a model in which OmpR binds to DNA in a head-to-head orientation, in contrast to the previously proposed asymmetric head-to-tail model. They also raise the possibility that OmpR may be capable of adopting more than one orientation as it binds to a vast array of genes to activate or repress transcription.

Bacterial Proteins↗
PubMed2006

The folding energy landscape of the dimerization domain of Escherichia coli Trp repressor: a joint experimental and theoretical investigation.

Enhanced structural insights into the folding energy landscape of the N-terminal dimerization domain of Escherichia coli tryptophan repressor, [2-66]2 TR, were obtained from a combined experimental and theoretical analysis of its equilibrium folding reaction. Previous studies have shown that the three intertwined helices in [2-66]2 TR are sufficient to drive the formation of a stable dimer for the full-length protein, [2-107]2 TR. The monomeric and dimeric folding intermediates that appear during the folding reactions of [2-66]2 TR have counterparts in the folding mechanism of the full-length protein. The equilibrium unfolding energy surface on which the folding and dimerization reactions occur for [2-66]2 TR was examined with a combination of native-state hydrogen exchange analysis, pepsin digestion and matrix-assisted laser/desorption mass spectrometry performed at several concentrations of protein and denaturant. Peptides corresponding to all three helices in [2-66]2 TR show multi-layered protection patterns consistent with the relative stabilities of the dimeric and monomeric folding intermediates. The observation of protection exceeding that offered by the dimeric intermediate in segments from all three helices implies that a segment-swapping mechanism may be operative in the monomeric intermediate. Protection greater than that expected from the global stability for a single amide hydrogen in a peptide from the C-helix possibly and another from the A-helix may reflect non-random structure, possibly a precursor for segment swapping, in the urea-denatured state. Native topology-based model simulations that correspond to a funnel energy landscape capture both the monomeric and dimeric intermediates suggested by the HX MS data and provide a rationale for the progressive acquisition of secondary structure in their conformational ensembles.

Amino Acid Sequence↗
PubMed2003

The role of the methylene blue and toluidine blue monomers and dimers in the photoinactivation of bacteria.

The interactions between the phenothiazine dyes, methylene blue (MB) and toluidine blue (TB), and bacteria (Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis, Hemophilus influenzae, Escherichia coli and Pseudomonas aeruginosa) were studied spectrophotometrically. This demonstrated that a metachromatic reaction took place between the dyes and bacteria. Furthermore, bacteria induced additional dimerization of MB and TB. The effective dimerization constants of MB and TB were evaluated in the presence of each bacterial strain at a concentration of 10(8) CFU/ml. The analysis of the effective dimerization constants for MB and TB in the presence of bacteria indicated that the ability to form dimers was greater for TB than for MB. Gram-negative bacteria induced the dye dimerization more intensely than gram-positive bacteria. There was a correlation between the ability of each dye to form dimers in the presence of bacteria and the relative photobactericidal efficacy of each dye against these bacteria. These results provide evidence confirming the essential role of the dye dimers in bacterial photodamage.

Bacteria↗
PubMed2005

A protein canyon in the FGF-FGF receptor dimer selects from an à la carte menu of heparan sulfate motifs.

Heparan sulfate (HS) is an essential and dynamic regulator of fibroblast growth factor (FGF) signaling. Two fundamentally different crystallographic models have been proposed to explain, at the molecular level, how HS/heparin enables FGF and FGF receptor (FGFR) to assemble into a functional dimer on the cell surface. In the symmetric 'two-end' model, the heparin-binding sites of FGF and FGFR merge to form a basic canyon that recruits two HS for binding. Within this canyon, the HS molecules primarily act to orchestrate and fortify multivalent and cooperative protein-protein contacts within the dimer that are the foundations of dimerization. In contrast, in the asymmetric model, which mechanistically resembles the previously proposed trans FGF dimer model, a single heparin molecule facilitates dimerization by cross-linking two FGFs into a trans dimer that brings together the two FGFRs. Interestingly, the crystal structure upon which the asymmetric model is based contains a symmetric dimer reminiscent of the symmetric two-end model, suggesting that a different interpretation of the crystal structure has led to the postulation of the asymmetric model. Importantly, the symmetric two-end model provides an intriguing solution to the problem of how HS selectivity is achieved in FGF signaling. The model reveals that, within the canyon, FGF and FGFR no longer adhere to their individual HS binding specificities, but instead act in unison to search for a unique HS motif from a plethora of HS epitopes that are expressed in a tissue-specific and developmentally regulated fashion. Primary sequence differences within the heparin-binding sites of FGFs and FGFRs, together with ligand-induced changes in FGFR conformation, lead to the formation of distinct canyons with unique HS specificity for individual FGF-FGFR complexes.

Animals↗
PubMed2004

Flipping the switch from monomeric to dimeric CV-N has little effect on antiviral activity.

Cyanovirin-N can exist in solution in monomeric and domain-swapped dimeric forms, with HIV-antiviral activity being reported for both. Here we present results for CV-N variants that form stable solution dimers: the obligate dimer [DeltaQ50]CV-N and the preferential dimer [S52P]CV-N. These variants exhibit comparable DeltaG values (10.6 +/- 0.5 and 9.4 +/- 0.5 kcal.mol(-1), respectively), similar to that of stabilized, monomeric [P51G]CV-N (9.8 +/- 0.5 kcal.mol(-1)), but significantly higher than wild-type CV-N (4.1 +/- 0.2 kcal.mol(-1)). During folding/unfolding, no stably folded monomer was observed under any condition for the obligate dimer [DeltaQ50]CV-N, whereas two monomeric, metastable species were detected for [S52P]CV-N at low concentrations. This is in contrast to our previous results for [P51G]CV-N and wild-type CV-N, for which the dimeric forms were found to be the metastable species. The dimeric mutants exhibit comparable antiviral activity against HIV and Ebola, similar to that of wild-type CV-N and the stabilized [P51G]CV-N variant.

Amino Acid Substitution↗