1aos
From Proteopedia
(New page: 200px<br /> <applet load="1aos" size="450" color="white" frame="true" align="right" spinBox="true" caption="1aos, resolution 4.2Å" /> '''HUMAN ARGININOSUCCIN...) |
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| - | [[Image:1aos.gif|left|200px]]<br /> | + | [[Image:1aos.gif|left|200px]]<br /><applet load="1aos" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1aos" size=" | + | |
caption="1aos, resolution 4.2Å" /> | caption="1aos, resolution 4.2Å" /> | ||
'''HUMAN ARGININOSUCCINATE LYASE'''<br /> | '''HUMAN ARGININOSUCCINATE LYASE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Intragenic complementation has been observed at the argininosuccinate | + | Intragenic complementation has been observed at the argininosuccinate lyase (ASL) locus. Intragenic complementation is a phenomenon that occurs when a multimeric protein is formed from subunits produced by different mutant alleles of a gene. The resulting hybrid protein exhibits enzymatic activity that is greater than that found in the oligomeric proteins produced by each mutant allele alone. The mutations involved in the most successful complementation event observed in ASL deficiency were found to be an aspartate to glycine mutation at codon 87 of one allele (D87G) coupled with a glutamine to arginine mutation at codon 286 of the other (Q286R). To understand the structural basis of the Q286R:D87G intragenic complementation event at the ASL locus, we have determined the x-ray crystal structure of recombinant human ASL at 4. 0 A resolution. The structure has been refined to an R factor of 18. 8%. Two monomers related by a noncrystallographic 2-fold axis comprise the asymmetric unit, and a crystallographic 2-fold axis of space group P3121 completes the tetramer. Each of the four active sites is composed of residues from three monomers. Structural mapping of the Q286R and D87G mutations indicate that both are near the active site and each is contributed by a different monomer. Thus when mutant monomers combine randomly such that one active site contains both mutations, it is required by molecular symmetry that another active site exists with no mutations. These "native" active sites give rise to the observed partial recovery of enzymatic activity. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1AOS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Argininosuccinate_lyase Argininosuccinate lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.3.2.1 4.3.2.1] Full crystallographic information is available from [http:// | + | 1AOS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Argininosuccinate_lyase Argininosuccinate lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.3.2.1 4.3.2.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AOS OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Howell, P | + | [[Category: Howell, P L.]] |
| - | [[Category: Mcinnes, R | + | [[Category: Mcinnes, R R.]] |
[[Category: Simpson, A.]] | [[Category: Simpson, A.]] | ||
| - | [[Category: Turner, M | + | [[Category: Turner, M A.]] |
[[Category: arginine biosynthesis]] | [[Category: arginine biosynthesis]] | ||
[[Category: lyase]] | [[Category: lyase]] | ||
[[Category: urea cycle]] | [[Category: urea cycle]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:46:46 2008'' |
Revision as of 09:46, 21 February 2008
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HUMAN ARGININOSUCCINATE LYASE
Contents |
Overview
Intragenic complementation has been observed at the argininosuccinate lyase (ASL) locus. Intragenic complementation is a phenomenon that occurs when a multimeric protein is formed from subunits produced by different mutant alleles of a gene. The resulting hybrid protein exhibits enzymatic activity that is greater than that found in the oligomeric proteins produced by each mutant allele alone. The mutations involved in the most successful complementation event observed in ASL deficiency were found to be an aspartate to glycine mutation at codon 87 of one allele (D87G) coupled with a glutamine to arginine mutation at codon 286 of the other (Q286R). To understand the structural basis of the Q286R:D87G intragenic complementation event at the ASL locus, we have determined the x-ray crystal structure of recombinant human ASL at 4. 0 A resolution. The structure has been refined to an R factor of 18. 8%. Two monomers related by a noncrystallographic 2-fold axis comprise the asymmetric unit, and a crystallographic 2-fold axis of space group P3121 completes the tetramer. Each of the four active sites is composed of residues from three monomers. Structural mapping of the Q286R and D87G mutations indicate that both are near the active site and each is contributed by a different monomer. Thus when mutant monomers combine randomly such that one active site contains both mutations, it is required by molecular symmetry that another active site exists with no mutations. These "native" active sites give rise to the observed partial recovery of enzymatic activity.
Disease
Known disease associated with this structure: Argininosuccinic aciduria OMIM:[608310]
About this Structure
1AOS is a Single protein structure of sequence from Homo sapiens. Active as Argininosuccinate lyase, with EC number 4.3.2.1 Full crystallographic information is available from OCA.
Reference
Human argininosuccinate lyase: a structural basis for intragenic complementation., Turner MA, Simpson A, McInnes RR, Howell PL, Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9063-8. PMID:9256435
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