onr:"swepub:oai:lup.lub.lu.se:def7e5c1-7590-4fc3-beda-8a88e502f4e7"
Sökning: onr:"swepub:oai:lup.lub.lu.se:def7e5c1-7590-4fc3-beda-8a88e502f4e7" > Leukotriene A(4) hy...
- 1 av 1
- Föregående post
- Nästa post
- Till träfflistan
| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 03787naa a2200361 4500 | |
| 001 | oai:lup.lub.lu.se:def7e5c1-7590-4fc3-beda-8a88e502f4e7 | |
| 003 | SwePub | |
| 008 | 160401s2004 | |||||||||||000 ||eng| | |
| 009 | oai:prod.swepub.kib.ki.se:13272484 | |
| 024 | 7 | a https://lup.lub.lu.se/record/1393932 URI |
| 024 | 7 | a https://doi.org/10.1074/jbc.M4010312002 DOI |
| 024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:132724842 URI |
| 040 | a (SwePub)lud (SwePub)ki | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a art2 swepub-publicationtype |
| 072 | 7 | a ref2 swepub-contenttype |
| 100 | 1 | a Rudberg, P Cu Karolinska Institutet4 aut |
| 245 | 1 0 | a Leukotriene A(4) hydrolase - Identification of a common carboxylate recognition site for the epoxide hydrolase and aminopeptidase substrates |
| 264 | 1 | c 2004 |
| 520 | a Leukotriene ( LT) A(4) hydrolase is a bifunctional zinc metalloenzyme, which converts LTA(4) into the neutrophil chemoattractant LTB4 and also exhibits an anion-dependent aminopeptidase activity. In the x-ray crystal structure of LTA(4) hydrolase, Arg(563) and Lys(565) are found at the entrance of the active center. Here we report that replacement of Arg(563), but not Lys(565), leads to complete abrogation of the epoxide hydrolase activity. However, mutations of Arg(563) do not seem to affect substrate binding strength, because values of K-i for LTA(4) are almost identical for wild type and ( R563K) LTA(4) hydrolase. These results are supported by the 2.3-Angstrom crystal structure of (R563A) LTA(4) hydrolase, which does not reveal structural changes that can explain the complete loss of enzyme function. For the aminopeptidase reaction, mutations of Arg(563) reduce the catalytic activity (V-max = 0.3 - 20%), whereas mutations of Lys(565) have limited effect on catalysis (V-max = 58 - 108%). However, in (K565A)- and (K565M) LTA(4) hydrolase, i.e. mutants lacking a positive charge, values of the Michaelis constant for alanine-p-nitroanilide increase significantly (K-m = 480 - 640%). Together, our data indicate that Arg(563) plays an unexpected, critical role in the epoxide hydrolase reaction, presumably in the positioning of the carboxylate tail to ensure perfect substrate alignment along the catalytic elements of the active site. In the aminopeptidase reaction, Arg(563) and Lys(565) seem to cooperate to provide sufficient binding strength and productive alignment of the substrate. In conclusion, Arg(563) and Lys(565) possess distinct roles as carboxylate recognition sites for two chemically different substrates, each of which is turned over in separate enzymatic reactions catalyzed by LTA(4) hydrolase. | |
| 650 | 7 | a NATURVETENSKAPx Biologi0 (SwePub)1062 hsv//swe |
| 650 | 7 | a NATURAL SCIENCESx Biological Sciences0 (SwePub)1062 hsv//eng |
| 700 | 1 | a Tholander, Fu Karolinska Institutet4 aut |
| 700 | 1 | a Andberg, M4 aut |
| 700 | 1 | a Thunnissen, Marjoleinu Lund University,Lunds universitet,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH4 aut0 (Swepub:lu)mbfys-mo |
| 700 | 1 | a Haeggstrom, J Zu Karolinska Institutet4 aut |
| 710 | 2 | a Karolinska Institutetb Biokemi och Strukturbiologi4 org |
| 773 | 0 | t Journal of Biological Chemistryg 279:26, s. 27376-27382q 279:26<27376-27382x 1083-351Xx 0021-9258 |
| 856 | 4 | u http://dx.doi.org/10.1074/jbc.M401031200x freey FULLTEXT |
| 856 | 4 8 | u https://lup.lub.lu.se/record/139393 |
| 856 | 4 8 | u https://doi.org/10.1074/jbc.M401031200 |
| 856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:13272484 |
Hitta via bibliotek
- Journal of Biological Chemistry (Sök värdpublikationen i LIBRIS)
Till lärosätets databas
- 1 av 1
- Föregående post
- Nästa post
- Till träfflistan
Hitta mer i SwePub
- Av författaren/redakt...
- Rudberg, P C
- Tholander, F
- Andberg, M
- Thunnissen, Marj ...
- Haeggstrom, J Z
- Om ämnet
-
- NATURVETENSKAP
- NATURVETENSKAP
- och Biologi
- Artiklar i publikationen
- Journal of Biolo ...
- Av lärosätet
- Lunds universitet
- Karolinska Institutet
Sök utanför SwePub
- Sök vidare i:
- Google Book Search
- Google Scholar
Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.
- Copyright © LIBRIS - Nationella bibliotekssystem
- LIBRIS.kb.se
