PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “enzyme engineering”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 613 records · Page 34Linked to original sources

Ribosome display for improved biotherapeutic molecules.

Ribosome display presents an innovative in vitro technology for the rapid isolation and evolution of high-affinity peptides or proteins. Displayed proteins are bound to and recovered from target molecules in multiple rounds of selection in order to enrich for specific binding proteins. No transformation step is necessary, which could lead to a loss of library diversity. A cycle of display and selection can be performed in one day, enabling the existing gene repertoire to be rapidly scanned. Proteins isolated from the panning rounds can be further modified through random or directed molecular evolution for affinity maturation, as well as selected for characteristics such as protein stability, folding and functional activity. Recently, the field of display technologies has become more prominent due to the generation of new scaffolds for ribosome display, isolation of high-affinity human antibodies by phage display, and their implementation in the discovery of novel protein-protein interactions. Applications for this technology extend into the broad field of antibody engineering, proteomics, and synthetic enzymes for diagnostics and therapeutics in cancer, autoimmune and infectious diseases, neurodegenerative diseases and inflammatory disorders. This review highlights the role of ribosome display in drug discovery, discusses advantages and disadvantages of the system, and attempts to predict the future impact of ribosome display technology on the development of novel engineered biopharmaceutical products for biological therapies.

Animals↗

The final acylation step in taxol biosynthesis: cloning of the taxoid C13-side-chain N-benzoyltransferase from Taxus.

The formation of several acyl groups and an amide group of Taxol is catalyzed by regioselective CoA thioester-dependent acyltransferases. Several full-length acyltransferase sequences, obtained from a cDNA library constructed from mRNA isolated from Taxus cuspidata cells induced for Taxol production with methyl jasmonate, were individually expressed in Escherichia coli, from which a cDNA clone encoding a 3'-N-debenzoyl- 2'-deoxytaxol N-benzoyltransferase was identified. This recombinant enzyme catalyzes the stereoselective coupling of the surrogate substrate N-debenzoyl-(3'RS)-2'-deoxytaxol with benzoyl-CoA to form predominantly one 3'-epimer of 2'-deoxytaxol. The product 2'-deoxytaxol was confirmed by radio-HPLC,(1)H-NMR, and chemical ionization-MS. This enzymatic reaction constitutes the final acylation in the Taxol biosynthetic pathway. The full-length cDNA coding for the N-benzoyltransferase has an ORF of 1,323 nucleotides and encodes a 441-residue protein with a calculated molecular weight of 49,040. The recombinant enzyme expressed in E. coli has a pH optimum at 8.0, a k(cat) approximately 1.5 +/- 0.3 s(-1) and K(m) values of 0.42 mM and 0.40 mM for the N-deacylated taxoid and benzoyl-CoA, respectively. In addition to improving the production yields of Taxol in genetically engineered host systems, this enzyme provides a means of attaching modified aroyl groups to taxoid precursors for the purpose of improving drug efficacy.

Aldehyde-Ketone Transferases↗

Fabry disease: focus on cardiac manifestations and molecular mechanisms.

PATHOGENESIS: Fabry disease is an inherited lysosomal storage disorder caused by deficiency of the enzyme alpha-galactosidase A. The enzyme deficiency results in accumulation of glycosphingolipids in the lysosomes n nearly all cell types and tissues leading to a multisystem disease. MANIFESTATIONS include painful crisis, angiokeratomas, corneal dystrophy, and hypohydrosis. The severe renal, cerebrovascular, and cardiac involvement is predominantly responsible for premature mortality in Fabry patients. The disease is X-linked and manifests primarily in hemizygous males but also heterozygous females can be affected. CARDIAC INVOLVEMENT is frequent in Fabry disease. Patients develop hypertrophic cardiomyopathy, arrhythmias, conduction abnormalities, and valvular abnormalities. Although Fabry disease leads to a complex clinical syndrome, there are studies indicating that manifestations can be limited to the heart. The isolated cardiac variant of Fabry disease seems to be more common than previously thought: around 3-6% of male patients with left ventricular hypertrophy seem to suffer from this disease variant. ENZYME REPLACEMENT THERAPY: Recent advances in molecular biology and genetic engineering have enabled the development of enzyme replacement therapy in Fabry disease. Results from two independent therapy studies are indeed promising: Infusion of the enzyme preparation seems to be well tolerated and effective in catabolizing the lipid deposits. This enzyme replacement therapy could be one of the first examples for causal treatment of left ventricular hypertrophy. Therefore, early diagnosis of hypertrophy patients with the cardiac variant of Fabry disease is important.

Adolescent↗

Essential role of selenium in the catalytic activities of mammalian thioredoxin reductase revealed by characterization of recombinant enzymes with selenocysteine mutations.

Mammalian thioredoxin reductases (TrxR) are dimers homologous to glutathione reductase with a selenocysteine (SeCys) residue in the conserved C-terminal sequence -Gly-Cys-SeCys-Gly. We removed the selenocysteine insertion sequence in the rat gene, and we changed the SeCys(498) encoded by TGA to Cys or Ser by mutagenesis. The truncated protein having the C-terminal SeCys-Gly dipeptide deleted, expected in selenium deficiency, was also engineered. All three mutant enzymes were overexpressed in Escherichia coli and purified to homogeneity with 1 mol of FAD per monomeric subunit. Anaerobic titrations with NADPH rapidly generated the A(540 nm) absorbance resulting from the thiolate-flavin charge transfer complex characteristic of mammalian TrxR. However, only the SeCys(498) --> Cys enzyme showed catalytic activity in reduction of thioredoxin, with a 100-fold lower k(cat) and a 10-fold lower K(m) compared with the wild type rat enzyme. The pH optimum of the SeCys(498) --> Cys mutant enzyme was 9 as opposed to 7 for the wild type TrxR, strongly suggesting involvement of the low pK(a) SeCys selenol in the enzyme mechanism. Whereas H(2)O(2) was a substrate for the wild type enzyme, all mutant enzymes lacked hydroperoxidase activity. Thus selenium is required for the catalytic activities of TrxR explaining the essential role of this trace element in cell growth.

Amino Acid Sequence↗

The importance of DT-diaphorase and hypoxia in the cytotoxicity of RH1 in human breast and non-small cell lung cancer cell lines.

The diaziridiny/benzoquinone RH1 is shortly to enter a phase I clinical trial. The drug was originally designed as a substrate for the enzyme DT-diaphorase (DTD) such that metabolic activation of the drug would lead to toxicity. To evaluate this, we have measured the toxicity of RH1 in a pair of non-small cell lung cancer (NSCLC) cell lines of widely differing levels of DTD and in MDA231 breast cancer cells which have been engineered to overexpress DTD. In addition, we have explored the importance of the putative one-electron reductase, P450 reductase, by assessing the toxicity of RH1 in MDA231 cells engineered to overexpress the enzyme. All drug exposures were carried out under hypoxic and aerobic conditions. Those cells with the highest levels of DTD, i.e. D7 versus MDA231 wt and H460 versus H596, are substantially more sensitive to RH1 than the cell lines expressing low DTD activity. Those cells with the lowest levels of DTD activity, i.e. MDA231 wt, R4 and H596, show much greater sensitivity to RH1 under hypoxic conditions compared to aerobic conditions. Finally, overexpression of P450 reductase, i.e. comparing MDA231 wt with R4, has little, if any, impact on the toxicity of RH1 under hypoxic or aerobic conditions. In summary, RH1 can be effective in killing cells containing high levels of DTD and may be useful in treating tumors expressing this enzyme.

Aerobiosis↗

Uptake of alpha-(L)-iduronidase produced by retrovirally transduced fibroblasts into neuronal and glial cells in vitro.

The uptake of recombinant alpha-(L)-iduronidase into glial and neuronal cells, produced by retrovirally transduced NIH3T3 fibroblasts, was studied. We demonstrate that: (1) neuronal and glial cells take up alpha-(L)-iduronidase released into the medium by retrovirally transduced fibroblasts expressing high levels of alpha-(L)-iduronidase; (2) both glial and neuronal cells express the cation independent mannose-6-phosphate receptor responsible for lysosomal enzyme uptake; and (3) uptake of the lysosomal enzyme can be blocked by excess free mannose-6-phosphate, but not glucose-6-phosphate. Thus, various brain cells take up alpha-(L)-iduronidase, possibly through a cation independent mannose-6-phosphate receptor mediated pathway, and this uptake is higher in actively dividing or immature brain cells. Consequently, (1) neuronal metabolism ought to be capable of cross correction by enzyme provided by genetically engineered and transplanted cells provided by bone marrow transplantation (BMT); (2) that BMT could have a more beneficial effect on neurological function if performed as early as possible; and (3) given that the uptake mechanism of glial cells has a higher capacity, it might be easier to target diseases like the leukodystrophies in which lysosomal enzymes are needed in glial cells, compared to diseases where lysosomal enzymes ought to be delivered into neurons.

3T3 Cells↗

Expression of chicken liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in Escherichia coli.

Chicken liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase was expressed in E. coli by using a pET3a T7 RNA polymerase-based expression system and was purified to homogeneity. The kinase and bisphosphatase of the expressed bifunctional enzyme had kinetic properties identical to those of the native chicken liver enzyme. However, the kinase activity of the chicken liver enzyme was 7-fold higher, while the bisphosphatase activity was 50 percent lower than those of the rat liver enzyme. Cys-256 of the rat liver bisphosphatase domain is not conserved in the chicken liver enzyme. A site-directed mutation was engineered at Cys-256 of the rat liver enzyme and the results indicate that the variation of this residue is not responsible for the difference in fructose-2,6-bisphosphatase activity between the rat and chicken liver enzymes. It is postulated that the difference in the kinase/bisphosphatase activity ratios of these two enzymes results from differences in their NH2-terminal regions.

Animals↗

Homogeneous enzyme immunoassay modified for application to luminescence-based biosensors.

Application of immunoassay to biosensors for use in the point-of-care setting ideally requires immunoassay without separation steps and with small volumes of both sample and reagents. The suitability of cloned enzyme donor immunoassay (CEDIA), one of a few homogeneous immunoassays available, was investigated for application to biosensors. This method is based on the bacterial enzyme beta-galactosidase, which has been genetically engineered by others into two inactive fragments, enzyme donor (ED) and enzyme acceptor (EA). Association of the ED and EA fragments in the assay results in formation of active enzyme, which acts on substrate to generate a detectable signal. Sensitivity of commercially available CEDIA kits were compared, with respect to the sample and reagent volumes, using three different signal generation processes. The CEDIA kit for valproic acid and three substrates, a colorimetric (chlorophenol red-beta-D-galactopyranoside), a chemiluminescent (Lumi-Gal 530), and a bioluminescent (Beta-Glo Assay System), were employed in the study. Our results indicate that the high sensitivity of the bioluminogenic substrate, D-luciferin-O-beta-galactopyranoside, with short assay time and small volumes of sample and reagents required for the assay, simple handling, and relatively low expense, make this substrate, together with CEDIA, suitable for application to biosensors intended for drug and metabolite monitoring in the point-of-care setting.

Biosensing Techniques↗

Structure of chalcone synthase and the molecular basis of plant polyketide biosynthesis.

Chalcone synthase (CHS) is pivotal for the biosynthesis of flavonoid antimicrobial phytoalexins and anthocyanin pigments in plants. It produces chalcone by condensing one p-coumaroyl- and three malonyl-coenzyme A thioesters into a polyketide reaction intermediate that cyclizes. The crystal structures of CHS alone and complexed with substrate and product analogs reveal the active site architecture that defines the sequence and chemistry of multiple decarboxylation and condensation reactions and provides a molecular understanding of the cyclization reaction leading to chalcone synthesis. The structure of CHS complexed with resveratrol also suggests how stilbene synthase, a related enzyme, uses the same substrates and an alternate cyclization pathway to form resveratrol. By using the three-dimensional structure and the large database of CHS-like sequences, we can identify proteins likely to possess novel substrate and product specificity. The structure elucidates the chemical basis of plant polyketide biosynthesis and provides a framework for engineering CHS-like enzymes to produce new products.

Acyltransferases↗

Long-term and significant correction of brain lesions in adult mucopolysaccharidosis type VII mice using recombinant AAV vectors.

Most lysosomal storage diseases, including mucopolysaccharidosis, affect the central nervous system (CNS). They often induce severe and progressive mental retardation. Replacement therapy by purified enzyme infusions is a promising approach for the treatment of peripheral organs but without effect on CNS pathology because the enzyme cannot cross the blood-brain barrier. Intracranial injection of recombinant adeno-associated virus (AAV) vectors offers an alternative for sustained local enzyme delivery from genetically engineered cells. We stereotactically injected an AAV vector containing the human beta-glucuronidase cDNA into the striatum of adult mice severely affected by mucopolysaccharidosis type VII at the time of treatment. Six weeks later, beta-glucuronidase activity in the injected hemisphere was comparable to that of heterozygous mice, which have a normal phenotype. Areas staining positive for enzyme activity enlarged with time, representing more than 10% of the hemisphere volume by 16 weeks. A complete reversion of lysosomal storage lesions was evident in these areas, as well as in most neurons located in surrounding negative areas and in the noninjected hemisphere. Thus, a single intracerebral injection of AAV vectors could achieve a broad and sustained lysosomal enzyme delivery, allowing for stable reversion of storage lesions in a significant fraction of the adult brain.

Animals↗

Industrial biocatalysis.

The number of industrial processes for the synthesis of fine and commodity chemicals, pharmaceutical and agrochemical intermediates and drug substances utilizing biological catalysts continues to grow. The combination of new molecular biology techniques, such as directed evolution and pathway engineering, with new and efficient high-throughput screening methods is poised to bolster this field and further advance the contribution of biocatalysis to the chemical and the pharmaceutical industries.

Catalysis↗

Protein engineering of oxygenases for biocatalysis.

Oxygenase enzymes have seen limited practical applications because of their complexity, poor stabilities, and often low catalytic rates. However, their ability to perform difficult chemistry with high selectivity and specificity has kept oxygenases at the forefront of engineering efforts. Growing understanding of structure-function relationships and improved protein engineering methods are paving the way for applications of oxygenases in chemical synthesis and bioremediation.

Animals↗

Oxidation of buried cysteines is slow and an insignificant factor in the structural destabilization of staphylococcal nuclease caused by H2O2 exposure.

The oxidation of buried cysteine or methionine residues can destroy the enzyme activity of a protein by disrupting structure. Engineering in such an oxidatively triggered switch for enzyme activity would only be useful if the effects of substitution are relatively minor, while the effects of the oxidized side chain upon structure are significant and the oxidation relatively easy. To assess the feasibility of this strategy for controlling enzyme activity, the effects of such substitutions and their oxidation were studied in a well characterized model protein, staphylococcal nuclease. Stability and enzyme activity of the oxidized proteins was assessed and compared to the stability and enzyme activity of the unoxidized proteins. Cysteines were found to be generally well tolerated in buried positions but these mutants were not more destabilized than wild-type when oxidized. This shows that buried cysteines are difficult enough to oxidize that this is not likely to be a useful protein engineering strategy or a commonly used regulatory modification. Similar effects were observed for methionine.

Binding Sites↗

Advances in phytase research.

Since its discovery in 1907, a complex of technological developments has created a potential $500 million market for phytase as an animal feed additive. During the last 30 years, research has led to increased use of soybean meal and other plant material as protein sources in animal feed. One problem that had to be overcome was the presence of antinutritional factors, including phytate, in plant meal. Phytate phosphorus is not digested by monogastric animals (e.g., hogs and poultry), and in order to supply enough of this nutrient, additional phosphate was required in the feed ration. Rock phosphate soon proved to be a cost-effective means of supplying this additional phosphorus, and the excess phytin phosphorus could be disposed of easily with the animals' manure. However, this additional phosphorus creates a massive environmental problem when the land's ability to bind it is exceeded. Over the last decade, numerous feed studies have established the efficacy of a fungal phytase, A. niger NRRL 3135, to hydrolyze phytin phosphorus in an animal's digestive tract, which benefits the animal while reducing total phosphorus levels in manure. The gene for phytase has now been cloned and overexpressed to provide a commercial source of phytase. This monomeric enzyme, a type of histidine acid phophatase (HAP), has been characterized and extensively studied. HAPs are also found in other fungi, plants, and animals. Several microbial and plant HAPs are known to have significant phytase activity. A second A. niger phytase (phyB), a tetramer, is known and, like phyA, has had its X-ray crystal structure determined. The model provided by this crystal structure research has provided an enhanced understanding of how these molecules function. In addition to the HAP phytase, several other phytases that lack the unique HAP active site motif RHGXRXP have been studied. The best known group of the non-HAPs is phytase C (phyC) from the genus Bacillus. While a preliminary X-ray crystallographic analysis has been initiated, no enzymatic mechanism has been proposed. Perhaps the pivotal event in the last century that created the need for phytase was the development of modern fertilizers after the Second World War. This fostered a transformation in agriculture and a tremendous increase in feed-grain production. These large quantities of cereals and meal in turn led to the transition of one segment of agriculture into "animal agriculture," with their its animal production capability. The huge volumes of manure spawned by these production units in time exceeded both the capacity of their crops and crop lands to utilize or bind the increased amount of phosphorus. Nutrient runoff from this land has now been linked to a number of blooms of toxin-producing microbes. Fish kills associated with these blooms have attracted public and governmental concern, as well as greater interest in phytase as a means to reduce this phosphorus pollution. Phytase research efforts now are focused on the engineering of an improved enzyme. Improved heat tolerance to allow the enzyme to survive the brief period of elevated temperature during the pelletization process is seen as an essential step to lower its cost in animal feed. Information from the X-ray crystal structure of phytase is also relevant to improving the pH optimum, substrate specificity, and enzyme stability. Several studies on new strategies that involve synergistic interactions between phytase and other hydrolytic enzymes have shown positive results. Further reduction in the production cost of phytase is also being pursued. Several studies have already investigated the use of various yeast expression systems as an alternative to the current production method for phytase using overexpression in filamentous fungi. Expression in plants is underway as a means to commercially produce phytase, as in biofarming in which plants such as alfalfa are used as "bioreactors," and also by developing plant cultivars that would produce enough transgenic phytase so that additional supplementation of their grain or meals is not necessary. Ultimately, transgenic poultry and hogs may produce their own digestive phytase. Another active area of current phytase research is expanding its usage. One area that offers tremendous opportunity is increasing the use of phytase in aquaculture. Research is currently centered on utilizing phytase to allow producers in this industry to switch to lower-cost plant protein in their feed formulations. Development of a phytase for this application could significantly lower production costs. Other areas for expanded use range from the use of phytase as a soil amendment, to its use in a bioreactor to generate specific myo-inositol phosphate species. The transformation of phytase into a peroxidase may lead to another novel use for this enzyme. As attempts are made to widen the use of phytase, it is also important that extended exposure and breathing its dust be avoided as prudent safety measures to avoid possible allergic responses. In expanding the use of phytase, another important consideration has been achieved. Conservation of the world's deposits of rock phosphate is recognized as important for future generations. Phosphorus is a basic component of life like nitrogen, but, unlike nitrogen, phosphorus does not have a cycle to constantly replenish its supply. It is very likely that the use of phytase will expand as the need to conserve the world's phosphate reserves increases.

6-Phytase↗

Engineering herbicide metabolism in tobacco and Arabidopsis with CYP76B1, a cytochrome P450 enzyme from Jerusalem artichoke.

The Jerusalem artichoke (Helianthus tuberosus) xenobiotic inducible cytochrome P450, CYP76B1, catalyzes rapid oxidative dealkylation of various phenylurea herbicides to yield nonphytotoxic metabolites. We have found that increased herbicide metabolism and tolerance can be achieved by ectopic constitutive expression of CYP76B1 in tobacco (Nicotiana tabacum) and Arabidopsis. Transformation with CYP76B1 conferred on tobacco and Arabidopsis a 20-fold increase in tolerance to linuron, a compound detoxified by a single dealkylation, and a 10-fold increase in tolerance to isoproturon or chlortoluron, which need successive catalytic steps for detoxification. Two constructs for expression of translational fusions of CYP76B1 with P450 reductase were prepared to test if they would yield even greater herbicide tolerance. Plants expressing these constructs had lower herbicide tolerance than CYP76B1 alone, which is apparently a consequence of reduced stability of the fusion proteins. In all cases, increased herbicide tolerance results from more extensive metabolism, as demonstrated with exogenously fed phenylurea. Beside increased herbicide tolerance, expression of CYP76B1 has no other visible phenotype in the transgenic plants. Our data indicate that CYP76B1 can function as a selectable marker for plant transformation, allowing efficient selection in vitro and in soil-grown plants. Plants expressing CYP76B1 may also be a potential tool for phytoremediation of contaminated sites.

7-Alkoxycoumarin O-Dealkylase↗

Genetically engineered bacteria: electrochemical sensing systems for antimonite and arsenite.

A bacterial sensing system that responds selectively to antimonite and arsenite has been investigated. The bacteria used in these studies have been genetically engineered to produce the enzyme beta-galactosidase in response to these ions. This is accomplished by using a plasmid that incorporates the gene for beta-galactosidase (reporter gene) under the control of the promoter of the ars operon. This plasmid also encodes for the ArsR protein, a regulatory protein of the ars operon, which, in the absence of antimonite or arsenite, restricts the expression of beta-galactosidase. In the presence of antimonite or arsenite the ArsR protein is released from the operator/ promoter region of the ars operon and beta-galactosidase is expressed. The activity of this enzyme was monitored electrochemically using p-aminophenyl beta-D-galactopyranoside as the substrate. The bacterial sensing system responds selectively to arsenite and antimonite (and to a lesser extent arsenate) and shows no significant response to phosphate, sulfate, nitrate, and carbonate.

Antimony↗

Unusual substrate specificity of a chimeric hypoxanthine-guanine phosphoribosyltransferase containing segments from the Plasmodium falciparum and human enzymes.

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) catalyzes the phosphoribosylation of hypoxanthine and guanine by transferring the phosphoribosyl moiety from phosphoribosylpyrophosphate (PRPP) on to N9 in the purine base, resulting in the formation of inosine monophosphate (IMP) and guanosine monophosphate (GMP). Xanthine is an additional substrate for the Plasmodium falciparum HGXPRT. Our aim has been to elucidate structural features in HGPRT that govern substrate specificity. We have addressed this problem by engineering chimeric HGPRTs, which contain segments from both the parasite and human enzymes. Four chimeric enzymes were engineered (DS1-DS4), of which the chimeric enzyme, DS1, in which the first 49 residues of human HGPRT were replaced with the corresponding residues from the P. falciparum enzyme, exhibited additional specificity for xanthine. None of the switched residues forms a part of the purine or PRPP binding region in the available crystal structures of HG(X)PRTs. Our data on the chimeric enzyme DS1 provide the first evidence that the N-terminal approximately 50 amino acids, although not proximal to the active site in the crystal structure, can in fact modulate substrate specificity. DS1 exhibits a reduced k(cat) for hypoxanthine and guanine, while its K(m) for these oxopurine bases remains largely unchanged. Its specific activity for xanthine is comparable with hypoxanthine but five times more than that for guanine.

Amino Acid Sequence↗

Expression of lignin peroxidase H8 in Escherichia coli: folding and activation of the recombinant enzyme with Ca2+ and haem.

An engineered cDNA from Phanerochaete chrysosporium encoding both the mature and pro-sequence regions of Lip isoenzyme H8 (Lip) has been successfully overexpressed in Escherichia coli. The recombinant protein (LipP*) was sequestered in inclusion bodies. The reduced-denatured polypeptide has been purified by differential solubilization, and the active enzyme recovered after controlled in vitro refolding (albeit in low yield), by glutathione-mediated oxidation of disulphides, in a folding medium containing an intermediate concentration of urea, Ca2+, and haem. The procedure is analogous to that previously described for the production of active recombinant horseradish peroxidase (HRP-C*) from inclusion-body material. It is quite possible, therefore, that this type of procedure may be suitable for the recovery of most, if not all, active recombinant peroxidases. The resultant LipP* has spectral characteristics identical with that of the native enzyme as isolated from Phanerochaete chrysosporium. Its specific activity measured in the standard veratryl alcohol (VA) assay was 39 micromol of VA oxidized/min per mg of protein, a value which compares extremely favourably with that of the native enzyme (36 micromol of VA/min per mg). Although levels of active enzyme obtained are not yet as high as in the case of HRP-C* (1% conversion of crude inactive LipP* polypeptide into pure fully active Lip), it is envisaged that further refinement of the expression/folding/activation procedures will provide sufficient protein for biophysical characterization of both the wild-type and site-directed mutants.

Base Sequence↗