Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50502 (Hip)
 7,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

s-ACE (the somatic form of angiotensin-converting enzyme) consists of two homologous domains (N- and C-domains), each bearing a catalytic site. Negative co-operativity between the two domains has been demonstrated for cow and pig ACEs. However, for the human enzyme there are conflicting reports in the literature: some suggest possible negative co-operativity between the domains, whereas others indicate independent functions of the domains within s-ACE. We demonstrate here that a 1:1 stoichiometry for the binding of the common ACE inhibitors, captopril and lisinopril, to human s-ACE is enough to abolish enzymatic activity towards FA {N-[3-(2-furyl)acryloyl]}-Phe-GlyGly, Cbz (benzyloxycarbonyl)-Phe-His-Leu or Hip (N-benzoylglycyl)-His-Leu. The kinetic parameters for the hydrolysis of seven tripeptide substrates by human s-ACE appeared to represent average values for parameters obtained for the individual N- and C-domains. Kinetic analysis of the simultaneous hydrolysis of two substrates, Hip-His-Leu (S1) and Cbz-Phe-His-Leu (S2), with a common product (His-Leu) by s-ACE at different values for the ratio of the initial concentrations of these substrates (i.e. sigma=[S2]0/[S1]0) demonstrated competition of these substrates for binding to the s-ACE molecule, i.e. binding of a substrate at one active site makes the other site unavailable for either the same or a different substrate. Thus the two domains within human s-ACE exhibit strong negative co-operativity upon binding of common inhibitors and in the hydrolysis reactions of tripeptide substrates.
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PMID:Kinetic probes for inter-domain co-operation in human somatic angiotensin-converting enzyme. 1603 30

Electrostatic interactions dominate the structure and free energy of biomolecules. To obtain accurate free energies involving charged groups from molecular simulations, OPLS-AA parameters have been reoptimized using Monte Carlo free energy perturbation. New parameters fit a self-consistent, experimental set of hydration free energies for acetate (Asp), propionate (Glu), 4-methylimidazolium (Hip), n-butylammonium (Lys), and n-propylguanidinium (Arg), all resembling charged residue side chains, including beta-carbons. It is shown that OPLS-AA free energies depend critically on the type of water model, TIP4P or TIP3P; i.e., each water model requires specific water-charged molecule interaction potentials. New models (models 1 and 3) are thus described for both water models. Uncertainties in relative free energies of charged residues are approximately 2 kcal/mol with the new parameters, due to variations in system setup (MAEs of ca. 1 kcal/mol) and noise from simulations (ca. 1 kcal/mol). The latter error of approximately 1 kcal/mol contrasts MAEs from standard OPLS-AA of up to 13 kcal/mol for the entire series of charged residues or up to 5 kcal/mol for the cationic series Lys, Arg, and Hip. The new parameters can be used directly in molecular simulations with no modification of neutral residues needed and are envisioned to be particular important in simulations where charged residues change environment.
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PMID:Improved interaction potentials for charged residues in proteins. 1820 48

We have compared four computer-assisted methods to measure penetration of the femoral head into the acetabular component in total hip replacement. These were the Martell Hip Analysis suite 7.14, Rogan HyperOrtho, Rogan View Pro-X and Roman v1.70. The images used for the investigation comprised 24 anteroposterior digital radiographs and 24 conventional acetate radiographs which were scanned to provide digital images. These radiographs were acquired from 24 patients with an uncemented total hip replacement with a follow-up of approximately eight years (mean 8.1; 6.3 to 9.1). Each image was measured twice by two blinded observers. The mean annual rates of penetration of the femoral head measured in the eight-year single image analysis were: Martell, 0.24 (SD 0.19); HyperOrtho, 0.12 (SD 0.08); View Pro-X, 0.12 (SD 0.06); Roman, 0.12 (SD 0.07). In paired analysis of the six-month and eight-year radiographs: Martell, 0.35 (SD 0.22); HyperOrtho, 0.15 (SD 0.13); View Pro-X, 0.11 (SD 0.06); Roman, 0.11 (SD 0.07). The intra- and inter-observer variability for the paired analysis was best for View Pro-X and Roman software, with intraclass correlations of 0.97, 0.87 and 0.96, 0.87, respectively, and worst for HyperOrtho and Martell, with intraclass correlations of 0.46, 0.13 and 0.33, 0.39, respectively. The Roman method proved the most precise and the most easy to use in clinical practice and the software is available free of charge. The Martell method showed the lowest precision, indicating a problem with its edge detection algorithm on digital images.
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PMID:The determination of linear and angular penetration of the femoral head into the acetabular component as an assessment of wear in total hip replacement: a comparison of four computer-assisted methods. 1859 89

Forty-four Holstein calves were fed a direct-fed microbial (DFM) and 1 of 2 milk replacers to evaluate calf performance and growth. Treatments were (1) a control milk replacer [22:20; 22% crude protein (CP) and 20% fat], (2) an accelerated milk replacer (27:10; 27% CP and 10% fat), (3) the control milk replacer with added DFM (22:20+D), and (4) the accelerated milk replacer with added DFM (27:10+D). Dry matter intake, rectal temperatures, respiration scores and rates, and fecal scores were collected daily. Body weight, hip and withers height, heart girth, blood, and rumen fluid samples were collected weekly. Effects of treatment, sex, week, and their interactions were analyzed. Calves fed an accelerated milk replacer, regardless of DFM supplementation, consumed more CP and metabolizable energy in the milk replacer. No treatment differences were found for starter intake or intake of neutral detergent fiber or acid detergent fiber in the starter. Calves fed the accelerated milk replacer had greater preweaning and weaning body weight compared with calves fed the control milk replacer. Average daily gain was greater during the preweaning period for calves fed the accelerated milk replacer, but the same pattern did not hold true during the postweaning period. Feed efficiency did not differ among treatments. Hip height tended to be and withers height and heart girth were greater at weaning for calves fed the accelerated milk replacer compared with calves fed the control milk replacer. Fecal scores were greatest in calves fed DFM. Overall acetate, propionate, butyrate, and n-valerate concentrations were lower in calves fed the accelerated milk replacer, but DFM did not have an effect. Rumen pH was not different. Blood metabolites were unaffected by DFM supplementation, but calves fed the accelerated milk replacer had increased partial pressure of CO2, bicarbonate, and total bicarbonate in the blood. Direct-fed microbial supplementation did not appear to benefit the calf in this trial.
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PMID:Short communication: Effects of increasing protein and energy in the milk replacer with or without direct-fed microbial supplementation on growth and performance of preweaned Holstein calves. 2520 Jul 91


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