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排序方式: 共有260条查询结果,搜索用时 15 毫秒
71.
Svante Pbo 《Trends in biochemical sciences》1999,24(12):1453-M16
The origin, history, and singularity of our species has fascinated storytellers, philosophers and scientists throughout, and doubtless before, recorded history. Anthropology, the modern-era discipline that deals with these issues, is a notoriously contentious field, perhaps because the topic at hand – the nature of our own species – is one that is difficult or impossible to approach in an unbiased way. Recently, molecular genetics has increasingly contributed to this field. Here, I briefly discuss three areas where I believe molecular studies are likely to be of decisive importance in the future. These concern the questions of where and when our species originated, what the genetic background for characters that differ between us and apes is, and how the phenotypic traits that vary among human groups have evolved. 相似文献
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73.
Lindstad RI Sylte I Mikalsen SO Seglen PO Berg E Winberg JO 《Journal of molecular biology》2005,350(4):682-698
In contrast to the prevalent view in the literature hitherto, the present study shows that pancreatic trypsin can activate human promatrix metalloproteinase-2 (proMMP-2). It is shown that trypsin's ability to activate proMMP-2 is dependent on various environmental factors such as the level of exogenously added Ca(2+) and Brij-35, temperature, as well as trypsin concentration. The activation occurred as a sequential processing of the proenzyme, initially generating an active 62kDa species. This was followed by successive truncation of the C-terminal domain, giving rise to active species of 56kDa, 52kDa and 50kDa. Tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) prevented the trypsin-mediated C-terminal truncation, without affecting the generation of the 62kDa species, while the presence of EDTA increased the rate of the trypsin-mediated activation of proMMP-2. MALDI-TOF MS analysis of the 50kDa form indicated that trypsin generated active forms with either Lys87 or Trp90 as the N-terminal residue and Arg538 as a C-terminal residue. The trypsin-activated MMP-2 was active in solution against both synthetic and physiologic substrates, and the steady-state kinetic coefficients k(cat), K(m) and k(cat)/K(m) were determined for the enzyme activated either by APMA, membrane-type 1 matrix metalloproteinase (MT1-MMP) or trypsin. The trypsin-activated MMP-2 exhibited slightly lower k(cat) and k(cat)/K(m) values as well as a slightly higher K(i) value against TIMP-1 compared to the enzyme activated by APMA or MT1-MMP. Docking studies of TIMP-1 revealed that the slightly weaker binding of the inhibitor to the trypsin-activated MMP-2 could be attributed to its shorter N terminus (Lys87/Trp90 versus Tyr81), as Phe83 and Arg86 interacted directly with the inhibitor. Our results suggest that the trypsin-activated MMP-2 possesses the catalytic and regulatory potential to be of significance in vivo. 相似文献
74.
Benach J Winberg JO Svendsen JS Atrian S Gonzàlez-Duarte R Ladenstein R 《Journal of molecular biology》2005,345(3):579-598
Drosophila alcohol dehydrogenase (DADH) is an NAD+-dependent enzyme that catalyzes the oxidation of alcohols to aldehydes/ketones and that is also able to further oxidize aldehydes to their corresponding carboxylic acids. The structure of the ternary enzyme-NADH-acetate complex of the slow alleloform of Drosophila melanogaster ADH (DmADH-S) was solved at 1.6 A resolution by X-ray crystallography. The coenzyme stereochemistry of the aldehyde dismutation reaction showed that the obtained enzyme-NADH-acetate complex reflects a productive ternary complex although no enzymatic reaction occurs. The stereochemistry of the acetate binding in the bifurcated substrate-binding site, along with previous stereochemical studies of aldehyde reduction and alcohol oxidation shows that the methyl group of the aldehyde in the reduction reaction binds to the R1 and in the oxidation reaction to the R2 sub-site. NMR studies along with previous kinetic studies show that the formed acetaldehyde intermediate in the oxidation of ethanol to acetate leaves the substrate site prior to the reduced coenzyme, and then binds to the newly formed enzyme-NAD+ complex. Here, we compare the three-dimensional structure of D.melanogaster ADH-S and a previous theoretically built model, evaluate the differences with the crystal structures of five Drosophila lebanonensis ADHs in numerous complexed forms that explain the substrate specificity as well as subtle kinetic differences between these two enzymes based on their crystal structures. We also re-examine the electrostatic influence of charged residues on the surface of the protein on the catalytic efficiency of the enzyme. 相似文献
75.
Lindon JC Nicholson JK Holmes E Keun HC Craig A Pearce JT Bruce SJ Hardy N Sansone SA Antti H Jonsson P Daykin C Navarange M Beger RD Verheij ER Amberg A Baunsgaard D Cantor GH Lehman-McKeeman L Earll M Wold S Johansson E Haselden JN Kramer K Thomas C Lindberg J Schuppe-Koistinen I Wilson ID Reily MD Robertson DG Senn H Krotzky A Kochhar S Powell J van der Ouderaa F Plumb R Schaefer H Spraul M;Standard Metabolic Reporting Structures working group 《Nature biotechnology》2005,23(7):833-838
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Ancient DNA analyses reveal high mitochondrial DNA sequence diversity and parallel morphological evolution of late pleistocene cave bears 总被引:6,自引:1,他引:5
Hofreiter M Capelli C Krings M Waits L Conard N Münzel S Rabeder G Nagel D Paunovic M Jambrĕsić G Meyer S Weiss G Pääbo S 《Molecular biology and evolution》2002,19(8):1244-1250
Cave bears (Ursus spelaeus) existed in Europe and western Asiauntil the end of the last glaciation some 10,000 years ago.To investigate the genetic diversity, population history, andrelationship among different cave bear populations, we havedetermined mitochondrial DNA sequences from 12 cave bears thatrange in age from about 26,500 to at least 49,000 years andoriginate from nine caves. The samples include one individualfrom the type specimen population, as well as two small-sizedhigh-Alpine bears. The results show that about 49,000 yearsago, the mtDNA diversity among cave bears was about 1.8-foldlower than the current species-wide diversity of brown bears(Ursus arctos). However, the current brown bear mtDNA gene poolconsists of three clades, and cave bear mtDNA diversity is similarto the diversity observed within each of these clades. The resultsalso show that geographically separated populations of the high-Alpinecave bear form were polyphyletic with respect to their mtDNA.This suggests that small size may have been an ancestral traitin cave bears and that large size evolved at least twice independently. 相似文献
78.
Kaessmann H Zöllner S Gustafsson AC Wiebe V Laan M Lundeberg J Uhlén M Pääbo S 《American journal of human genetics》2002,70(3):673-685
The extent of linkage disequilibrium (LD) was studied in two small food-gathering populations—Evenki and Saami—and two larger food-producing populations—Finns and Swedes—in northern Eurasia. In total, 50 single-nucleotide polymorphisms (SNPs) from five genes were genotyped using real-time pyrophosphate DNA sequencing, whereas 14 microsatellites were genotyped in two X-chromosomal regions. In addition, hypervariable region I of the mtDNA was sequenced to shed light on the demographic history of the populations. The SNP data, as well as the microsatellite data, reveal extensive levels of LD in Evenki and Saami when compared to Finns and Swedes. mtDNA-sequence variation is compatible with constant population size over time in Evenki and Saami but indicates population expansion in Finns and Swedes. Furthermore, the similarity between Finns and Swedes in SNP allele- and haplotype-frequency distributions indicate that these two populations may share a recent common origin. These findings suggest that populations such as the Evenki and the Saami, rather than the Finns, may be particularly suited for the initial coarse mapping of common complex diseases. 相似文献
79.
The transmembrane protein Off-track associates with Plexins and functions downstream of Semaphorin signaling during axon guidance 总被引:4,自引:0,他引:4
The Plexin family of transmembrane proteins appears to function as repulsive receptors for most if not all Semaphorins. Here, we use genetic and biochemical analysis in Drosophila to show that the transmembrane protein Off-track (OTK) associates with Plexin A, the receptor for Sema 1a, and that OTK is a component of the repulsive signaling response to Semaphorin ligands. In vitro, OTK associates with Plexins. In vivo, mutations in the otk gene lead to phenotypes resembling those of loss-of-function mutations of either Sema1a or PlexA. The otk gene displays strong genetic interactions with Sema1a and PlexA, suggesting that OTK and Plexin A function downstream of Sema 1a. 相似文献
80.