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1.
Sandford R; Sgotto B; Aparicio S; Brenner S; Vaudin M; Wilson RK; Chissoe S; Pepin K; Bateman A; Chothia C; Hughes J; Harris P 《Human molecular genetics》1997,6(9):1483-1489
PKD1 is the major locus of the common genetic disorder autosomal dominant
polycystic kidney disease (ADPKD). Analysis of the predicted protein
sequence of the human PKD1 gene, polycystin, shows a large molecule with a
unique arrangement of extracellular domains and multiple putative
transmembrane regions. The precise function of polycystin remains unclear
with a paucity of mutations to define key structural and functional
domains. To refine the structure of this protein we have cloned the genomic
region encoding the Fugu PKD1 gene. Fugu PKD1 spans 36 kb of genomic DNA
and has greater complexity with 54 exons compared with 46 in man.
Comparative analysis of the predicted protein sequences shows a lower level
of homology than in similar studies with identity of 40 and 59% similarity.
However key structural motifs including leucine rich repeats (LRR), a
C-type lectin and LDL-A like domains and 16 PKD repeats are maintained. A
region of homology with the sea urchin REJ protein was also confirmed in
Fugu but found to extend over 1000 amino acids. Several highly conserved
intra- and extra- cellular regions, with no known sequence homologies, that
are likely to be of functional importance were detected. The likely
structure of the membrane associated region has been refined with
similarity to the PKD2 protein and voltage gated Ca2+ and Na+ channels
highlighted over part of this area. The overall protein structure has
therefore been clarified and this comparative analysis derived structure
will form the basis for the functional study of polycystin and its
individual domains.
相似文献
2.
C Chothia S Wodak J Janin 《Proceedings of the National Academy of Sciences of the United States of America》1976,73(11):3793-3797
We calculate the surface area buried in subunit interfaces of human deoxyhemoglobin and of horse methemoglobin. A larger surface area is buried in deoxy- than in methemoglobin as a result of tertiary and quaternary structure changes. In both molecules the dimer-dimer interface is closepacked. This implies that hydrophobicity stabilizes the deoxystructure, the free energy spent in keeping the subunits in a low-affinity conformation being compensated by hydrophobic free energy due to the smaller surface area accessible to solvent. 相似文献
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Mogamat-Yazied Chothia Mogamat Razeen Davids Raisa Bhikoo 《World Journal of Nephrology》2018,7(7):143-147
Renal artery stenosis is a common cause of secondary hypertension and chronic kidney disease. We present here a case of fibromuscular dysplasia that was treated with surgical revascularization, resulting in recovery of kidney function with eventual cessation of chronic dialysis. The case involves a 25-year-old female with coincidentally discovered hypertension, who underwent further investigations revealing a diagnosis of renal artery stenosis due to fibromuscular dysplasia. She subsequently developed two episodes of malignant hypertension, with flash pulmonary oedema and worsening renal failure that resulted in dialysis dependence. After evidence was obtained that the right kidney was still viable, a revascularization procedure was performed, improving blood pressure control and restoring kidney function, thereby allowing dialysis to be stopped. This case highlights the importance of evaluating patients with renal artery stenosis for revascularization before committing them to a life of chronic dialysis. 相似文献
5.
The study assessed the knowledge of mothers of the high income group of urban Baroda, related to breast feeding and weaning.
Forty mothers with children aged 4 to 18 months were studied. Knowledge and practices regarding breast feeding and weaning
were assessed using pretested questionnaires. Results indicated that only half the mothers breast fed their babies on the
first day. Breast feeding was stopped when the child was 3–6 months; top feeding and solid supplements were initiated at 4–6
months. Mainly commercial baby foods were used for weaning.Most mothers avoided ‘dals’ for the child because these were believed
to be difficult to digest and produced gas in the child’s stomach. Fifty percent of the mothers were not in favour of feeding
the sick child with small frequent meals. 相似文献
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Cyrus Chothia Peter Pauling 《Proceedings of the National Academy of Sciences of the United States of America》1970,65(3):477-482
A correlation of the crystal structure analyses of the potent nicotinic agonists acetylcholine, acetyl-alpha-methylcholine, lactoylcholine, 1,1-dimethyl-4-phenylpiperazine, and nicotine allows one to determine the conformation of cholinergic agonists relevant to nicotinic nerve receptors. 相似文献
8.
Cyrus Chothia Peter Pauling 《Proceedings of the National Academy of Sciences of the United States of America》1969,63(4):1063-1070
There are only a few possible conformations of D-lysergic acid diethylamide and hallucinogenic derivatives of tryptamine and phenylethylamine. Of these possible conformations there is a high structural correlation among the probable conformations of active hallucinogenic molecules and between these conformations and the known conformations of several central nervous system transmitter molecules. 相似文献
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C Chothia M Levitt D Richardson 《Proceedings of the National Academy of Sciences of the United States of America》1977,74(10):4130-4134
Simple models are presented that describe the rules for almost all the packing that occurs between and among alpha-helices and pleated sheets. These packing rules, together with the primary and secondary structures, are the major determinants of the three-dimensional structure of proteins. 相似文献