Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344329 (collapse)
 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to obtain an early prediction for segmental collapse of the femoral head after femoral neck fracture, we have studied in 53 cases of the femoral neck fracture using 99mTC-MDP scintimetry. According to the radionuclide uptake ratio of the femoral heads, we can estimate the gravity of the avascular necrosis of the femoral head after fracture and recognize the repair process in the necrotic head. Fifty-three cases of fresh fracture were examined by sequential scintigraphy before operation and during follow up examinations after operation. The radionuclide uptake were all increased in 3 to 4 months after operation as comparing with that done before operation. The uptake ratios in 37 cases decreased gradually and approached 1 in 12 months after operation. All of them have an excellent result during follow up examination 36 months after surgery. The uptake ratios in 19 cases were also increased after operation, but still maintained at a high level in 6 to 12 months. They all showed radiographical signs of segmental collapse 18 to 24 months after operation. These results showed that uptake ratio of the radionuclide bone imaging is able to predict the occurrence of segmental collapse of the femoral head after femoral neck fracture. The time of the diagnosis by scintigraphy for segmental collapse of the femoral head is earlier than that by radiography.
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PMID:[Early diagnosis by scintigraphy of segmental collapse of the femur head following femur neck fracture]. 779 84

An analysis of the X-ray structure of cilastatin bound to membrane dipeptidase, together with docking studies, is presented here to reveal how a simple amide may act as a high-affinity, reversible, amidase inhibitor. Cilastatin binds as a normal substrate and is orientated in a perfect near-attack conformer for formation of a tetrahedral intermediate with the zinc-bound water/hydroxide. This intermediate is fated, however, only to revert to its starting components as scission of the amide bond is prevented by the precise fit of cilastatin within the active site. The cilastatin alkyl end groups that are tightly buttressed against amino acid residues on opposite sides of the active site, are aligned along the C-N reaction coordinate axis thereby preventing collapse of the intermediate via rupture of the C-N bond. Such a feature could have more general applicability in the explicit design of substrate variants as selective, tight-binding, and reversible inhibitors.
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PMID:A substrate variant as a high-affinity, reversible inhibitor: insight from the X-ray structure of cilastatin bound to membrane dipeptidase. 1261 84

Isoaspartyl dipeptidase (IAD) is a member of the amidohydrolase superfamily and catalyzes the hydrolytic cleavage of beta-aspartyl dipeptides. Structural studies of the wild-type enzyme have demonstrated that the active site consists of a binuclear metal center positioned at the C-terminal end of a (beta/alpha)(8)-barrel domain. Steady-state kinetic parameters for the hydrolysis of beta-aspartyl dipeptides were obtained at pH 8.1. The pH-rate profiles for the hydrolysis of beta-Asp-Leu were obtained for the Zn/Zn-, Co/Co-, Ni/Ni-, and Cd/Cd-substituted forms of IAD. Bell-shaped profiles were observed for k(cat) and k(cat)/K(m) as a function of pH for all four metal-substituted forms. The pK(a) of the group that must be unprotonated for catalytic activity varied according to the specific metal ion bound in the active site, whereas the pK(a) of the group that must be protonated for catalytic activity was relatively independent of the specific metal ion present. The identity of the group that must be unprotonated for catalytic activity was consistent with the hydroxide that bridges the two divalent cations of the binuclear metal center. The identity of the group that must be protonated for activity was consistent with the free alpha-amino group of the dipeptide substrate. Kinetic constants were obtained for the mutant enzymes at conserved residues Glu77, Tyr137, Arg169, Arg233, Asp285, and Ser289. The catalytic properties of the wild-type and mutant enzymes, coupled with the X-ray crystal structure of the D285N mutant complexed with beta-Asp-His, are consistent with a chemical reaction mechanism for the hydrolysis of dipeptides that is initiated by the polarization of the amide bond via complexation to the beta-metal ion of the binuclear metal center. Nucleophilic attack by the bridging hydroxide is facilitated by abstraction of its proton by the side chain carboxylate of Asp285. Collapse of the tetrahedral intermediate and cleavage of the carbon-nitrogen bond occur with donation of a proton from the protonated form of Asp285.
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PMID:Mechanism of the reaction catalyzed by isoaspartyl dipeptidase from Escherichia coli. 1588 50

Avascular necrosis (AVN) of bone is defined as the cellular death of bone components due to the interruption of the blood supply; the bone structures then collapse, resulting in pain and loss of joint function. Magnetic resonance imaging (MRI) is the gold standard to diagnose AVN. We present an unusual case of AVN of talus in a patient of thalassemia major that was diagnosed on the Tc-99m MDP bone scan with equivocal findings on MRI. Key Message: The diagnosis of AVN is primarily done using radiological investigations. However, the bone scan plays a role in the diagnosis in atypical presentations and should be considered when MRI is equivocal.
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PMID:Avascular Necrosis of Talus Diagnosed on Tc-99m MDP Bone Scan. 2868 Feb 6


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