The proteoglycan aggrecan is an important major component of cartilage matrix that gives articular the ability to withstand compression. Increased breakdown associated with development arthritis and considered be catalyzed by aggrecanases, members ADAM-TS family metalloproteinases. Four endogenous tissue inhibitors metalloproteinases (TIMPs) regulate activities functional (MMPs), enzymes degrade most components connective tissue, but no factors responsible for regulation aggrecanases have...

Errors in clinical decision-making are disturbingly common. Here, we show that structured information–sharing networks among clinicians significantly reduce diagnostic errors, and improve treatment recommendations, as compared to groups of ...Errors Recent studies have found 10 15% all decisions regarding diagnoses inaccurate. experimentally study the ability ...

The complete amino acid sequence of bovine α-lactalbumin has been established. unique was deduced by characterization the tryptic, chymotryptic, and peptic peptides isolated from enzymic hydrolysates two fragments obtained on cleavage S-aminoethyl-α-lactalbumin with cyanogen bromide as described earlier. Important overlapping were also analysis chymotryptic unmodified or S-carboxymethyl-α-lactalbumin. Bovine contains 123 residues NH2-terminal glutamic COOH-terminal leucine. In accord earlier...

A partial sequence for α-lactalbumin, one of the two proteins lactose synthetase, has been established. This includes exact position all but 15 123 residues in molecule, and four disulfide bonds. structure shows that α-lactalbumin a close structural similarity to hens egg white lysozyme. When sequences are aligned, 40 identical with corresponding An additional 27 at positions chemically similar. From these observations it is concluded genes lysozyme derived from common ancestor. It proposed...

Of the four known tissue inhibitors of metalloproteinases (TIMPs), TIMP-3 is distinguished by its tighter binding to extracellular matrix. The present results show that glycosaminoglycans such as heparin, heparan sulfate, chondroitin sulfates A, B, and C, sulfated compounds suramin pentosan efficiently extract from postpartum rat uterus. Enzymatic treatment heparinase III or chondroitinase ABC also releases TIMP-3, but neither one alone gives complete release. Confocal microscopy shows...

The amino acid sequences of seven cyanogen bromide fragments human serum transferrin have been determined, and the primary structure established by determining order these three additional (Sutton, M. R., MacGillivray, R. T. A., Brew, K. (1975) Eur.J. Biochem 51, 43-48) in polypeptide chain.The was deduced from peptides that overlap methionyl residues which were obtained thermolysin digestion performic acid-oxidized or partial peptic hydrolysis unmodified transferrin, together with other...

The milk protein β-lactoglobulin has been extensively studied but its function not identified. A clue regarding the of a can be obtained by discovering genetic relationship with known through comparisons amino acid sequence. Such revealed that is similar to human serum retinol-binding and another unknown as complex-forming glycoprotein heterogeneous in charge (protein HC). β-Lactoglobulins from several species have found bind retinol, while absorption fluorescence properties reported for...

Although the serum protein alpha 1-acid glycoprotein (AGP) or orosomucoid has been extensively studied, its relationships with other proteins have controversial and precise physiological function remained unclear. It is shown here that AGP significantly similar in amino acid sequence locations of introns structural gene to members a superfamily includes retinol-binding (RBP), beta-lactoglobulin (LG), 2u-globulin, HC (alpha 1-microglobulin). The view three-dimensional structure closely...

High affinity binding of Ca²⁺to α-lactalbumin (LA) stabilizes the native structure and is required for efficient generation protein with correct disulfide bonds from reduced denatured state. A progressive increase in LA conformers Ca²⁺ as they develop increasingly structures can account tendency apo form to assume a molten globule state large acceleration folding by Ca²⁺. To investigate effect calcium on bovine LA, x-ray have been determined crystals holo...

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Background: The regulation of milk lactose biosynthesis is highly dependent on the action a specifier protein, α-lactalbumin (LA). Together with glycosyltransferase, LA forms enzyme complex synthase. promotes binding glucose to and facilitates lactose. To gain further insight into molecular basis function in synthase we have determined structures three species variants LA.Results crystal guinea-pig, goat recombinant form bovine been using replacement techniques. Overall, are very similar...

Reactions catalyzed by human milk N-acetyl lactosamine synthetase in the presence and absence of ä-lactalbumins have been investigated steady-state kinetics. N-Acetyl synthesis lactose α-lactalbumin appear to proceed an ordered sequential reaction, with substrates attaching order: Mn2+, UDP-galactose monosaccharide. Under conditions used (pH 7.4, 37 °C) attachment Mn2+ is not at thermo-dynamic equilibrium it appears that enzyme can accept either free or its complex as substrate. Evidence...

The complete amino acid sequence of human serum transferrin has been determined by aligning the structures 10 CNBr fragments. order these fragments in polypeptide chain is deduced from peptides overlapping methionine residues and other evidence. Human contains 678 and--including two asparagine-linked glycans--has an overall molecular weight 79,550. homologous domains consisting 1-336 337-678, which 40% are identical when aligned inserting gaps at appropriate positions. Disulfide bond...

Galactosyltransferases constitute a family of enzymes, each member which transfers galactose from UDPgalactose to specific acceptor molecule, generating galactose-acceptor linkage. Two synthetic oligonucleotides, 27mer and 21mer, were synthesized, based on the amino acid sequences two peptides derived bovine milk N-acetylglucosaminide (beta 1-4)galactosyltransferase (EC 2.4.1.90), used as hybridization probes isolate cDNA clones for galactosyltransferase mammary gland library. One plasmids,...

The levels of the A and B proteins lactose synthetase were measured in organ cultures mouse mammary glands treated with different hormone combinations. Both stimulated specifically by insulin, hydrocortisone, prolactin. Prolactin, however, induced synthesis each protein when pretreated insulin hydrocortisone. Under these conditions there was a 10-fold increase activity 2-fold activity. Specific inhibitors prevented induction both When from mice at stages pregnancy, it found that level...

α‐Lactalbumin was isolated from human milk in a yield of 1.8 mg/ml milk. The purification procedure involved ammonium sulphate fractionation (30% to 80% saturation) and pH‐4.0 precipitation, followed by gel filtration with Sephadex G‐100. A final stage using DEAE‐cellulose necessary some preparations. Peptides derived the reduced, S ‐aminoethylated protein treatment cyanogen bromide digestion these CNBr fragments trypsin, chymotrypsin or thermolysin, were purified filtration, ion exchange...

produces a pronounced conformational change, as indicated by fluorescence and absorbance changes.These changes closely resemble the that occur on acid denaturation of native protein.The binding ions to apo-a-lactalbumin at pH 7.4 has been examined monitoring fluo- rescence direct measurements with 4SCaC12.The results indicate presence two Ca2+ sites apo-bovine a-lactalbumin, stronger site (K, 2.7 X lo6 M-') weaker (& 3.1 lo4 M-'); rebinding correlate saturation site.Mn2+ can also bind...

The cross-linking of the two components lactose synthetase, a-lactalbumin and a galactosyltransferase, with dimethylpimelimidate was examined.The extent crosslinking at pH 8.1 found to be dependent upon presence substrates or inhibitors for galactosyltransferase.N-acetylglucosamine mixtures either N-acetylglucosamine, Mn2+ UDP, UDP-galactose promoted formation cross-linked species.Glucose mixture UDP Mn*+ were much less effective in promoting cross-linking.Two types intermolecularly...

An approach is described to monitor directly at the level of individual residues formation structure during protein folding. A two-dimensional heteronuclear nuclear magnetic resonance (NMR) spectrum was recorded after rapid initiation refolding a labeled with nitrogen-15. The intensities and line shapes cross peaks in reflected kinetic time course folding events that occurred spectral accumulation. method used demonstrate cooperative nature acquisition native main chain fold apo bovine...