Serine dehydratase: Difference between revisions
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'''Serine Dehydratase''' or '''L-Serine Ammonia Lyase (SDH)''' is in the family of [[Pyridoxal_phosphate|Pyridoxal Phosphate-dependent (PLP)]] enzymes. SDH is found widely in nature, but its structural and chemical properties are considerably different from species to species. SDH is found in [[yeast]], [[bacteria]], and the [[cytoplasm]] of mammalian [[hepatocytes]]. The mechanism it catalyzes is the [[deamination]] of [[L-serine]] to yield [[pyruvate]] and [[ammonia]]. <ref>{{cite journal|last=Lei|first=Sun|coauthors=Mark Bartlam, Yiwei Liu, Hai Pang, Zihe Rao|title=Crystal structure of the pyridoxal-5′-phosphate-dependent serine dehydratase from human liver|journal=Protein Science|year=2005|month=March|volume=14|series=3|pages=791–798|pmid=PMC2279282|url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2279282/pdf/0140791.pdf|accessdate=17 May 2011}}</ref> |
'''Serine Dehydratase''' or ''' [[L-serine_ammonia-lyase|L-Serine Ammonia Lyase]] (SDH)''' is in the family of [[Pyridoxal_phosphate|Pyridoxal Phosphate-dependent (PLP)]] enzymes. SDH is found widely in nature, but its structural and chemical properties are considerably different from species to species. SDH is found in [[yeast]], [[bacteria]], and the [[cytoplasm]] of mammalian [[hepatocytes]]. The mechanism it catalyzes is the [[deamination]] of [[L-serine]] and [[L-threonine]] to yield [[pyruvate]] and [[α-ketobutyrate]] respectively, with the release of [[ammonia]] in both cases. <ref name="Crystal structure">{{cite journal|last=Lei|first=Sun|coauthors=Mark Bartlam, Yiwei Liu, Hai Pang, Zihe Rao|title=Crystal structure of the pyridoxal-5′-phosphate-dependent serine dehydratase from human liver|journal=Protein Science|year=2005|month=March|volume=14|series=3|pages=791–798|pmid=PMC2279282|url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2279282/pdf/0140791.pdf|accessdate=17 May 2011}}</ref> |
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'''Serine dehydratase''' is an enzyme that converts [[serine]] to [[pyruvate]]. |
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Conversion of L-serine and L-threonine to pyruvate and α-ketobutyrate, respectively. |
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It also converts [[Threonine]] to [[Propionyl CoA]]. |
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This enzyme has 1 [[substrate]], [[L-Serine]], and two [[products]], [[pyruvate]] and [[ammonia|NH<sub>3</sub>]], and uses 1 [[cofactor]], [[pyridoxal phosphate]] (PLP). |
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==Nomenclature== |
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Serine Dehydratase is also known as<ref>{{cite web|title=KEGG ENZYME Database Entry|url=http://www.genome.jp/dbget-bin/www_bget?enzyme+4.3.1.17|work=Kyoto Encyclopedia of Genes and Genomes|publisher=Kanehisa Laboratories|accessdate=17 May 2011}}</ref>: |
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L-serine ammonia-lyase |
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Serine deaminase |
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L-hydroxyaminoacid dehydratase |
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L-serine deaminase |
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L-serine dehydratase |
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L-serine hydro-lyase |
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==Enzyme Structure== |
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'''HoloEnzyme:''' |
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The [[holoenzyme]] SDH contains 319 [[residues]], 1 [[PLP]] [[cofactor]] molecule, and 131 [[water]] molecules1. The overall fold of the [[monomer]] is very similar to that of other [[PLP-dependent enzymes]] of the Beta-family . The enzyme contains a large [[Protein domain|domain]] ([[catalytic]] domain or PLP- binding domain) and a small domain. The domains are joined by two peptide linkers (residues 32-35 and 138-146), with the internal gap created being the space for the [[active site]]<ref name="Crystal structure"/> (Figure 1). |
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'''Two Dimers:''' |
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Two [[monomers]] of hSDS (human SDH) come together to make a [[dimer]]. The interface between the two monomers is formed through [[hydrogen bonds]] and [[hydrophobic interactions]]. The monomer–monomer contacts involve six pairs of [[hydrogen bonds]] formed between 10 residues ([[Arg]]98-[[Asn]]260, [[Leu]]310-[[Asn]]260, and [[Leu]]265-[[Lys]]263). Additional interactions include a number of [[Hydrophobic residues|hydrophobic contacts]] between the residues [[Met]]17, [[Lys]]21, [[Asn]]101, [[Glu]]102, [[Ser]]306, [[Ile]]308, [[Ser]]309, and [[Ile]]264 in each [[monomer]].<ref name="Crystal structure"/> (Figure 2) |
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'''Cofactor Binding Site:''' |
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The [[PLP]] [[cofactor]] is positioned in between the [[Secondary structure of proteins|Beta-strands]] 7 and 10 of the large domain and lies on the large internal gap made between small and large domain. The [[cofactor]] is [[covalently]] bonded through a [[Schiff base|Schiff base linkage]] to [[Lys]]41. The [[cofactor]] is sandwiched between the side chain of [[Phe]]40 and the main chain of [[Ala]]222. Each of the polar substituents of PLP is coordinated by functional groups: the [[pyridinium]] nitrogen of PLP is hydrogen-bonded to the side chain of [[Cys]]303, the C3-hydroxyl group of PLP is hydrogen-bonded to the side chain of [[Asn]]67, and the [[phosphate group]] of [[PLP]] is coordinated by main chain amides from the [http://jb.asm.org/cgi/reprint/190/7/2556.pdf tetraglycine] loop.<ref name="Crystal structure"/> (Figure 3 and Figure 4) |
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==Enzyme Mechanism== |
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==Inhibitors== |
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==Biological Function== |
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==Disease Relevance== |
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==Evolution== |
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==Historical Significance== |
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==External links== |
==External links== |
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* {{MeshName|Serine+dehydratase}} |
* {{MeshName|Serine+dehydratase}} |
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Revision as of 03:06, 17 May 2011
| serine dehydratase | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | SDS | ||||||
| NCBI gene | 10993 | ||||||
| HGNC | 10691 | ||||||
| OMIM | 182128 | ||||||
| RefSeq | NM_006843 | ||||||
| UniProt | P20132 | ||||||
| Other data | |||||||
| EC number | 4.3.1.17 | ||||||
| Locus | Chr. 12 q24.21 | ||||||
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Serine Dehydratase or L-Serine Ammonia Lyase (SDH) is in the family of Pyridoxal Phosphate-dependent (PLP) enzymes. SDH is found widely in nature, but its structural and chemical properties are considerably different from species to species. SDH is found in yeast, bacteria, and the cytoplasm of mammalian hepatocytes. The mechanism it catalyzes is the deamination of L-serine and L-threonine to yield pyruvate and α-ketobutyrate respectively, with the release of ammonia in both cases. [1]
Conversion of L-serine and L-threonine to pyruvate and α-ketobutyrate, respectively.
This enzyme has 1 substrate, L-Serine, and two products, pyruvate and NH3, and uses 1 cofactor, pyridoxal phosphate (PLP).
Nomenclature
Serine Dehydratase is also known as[2]: L-serine ammonia-lyase Serine deaminase L-hydroxyaminoacid dehydratase L-serine deaminase L-serine dehydratase L-serine hydro-lyase
Enzyme Structure
HoloEnzyme: The holoenzyme SDH contains 319 residues, 1 PLP cofactor molecule, and 131 water molecules1. The overall fold of the monomer is very similar to that of other PLP-dependent enzymes of the Beta-family . The enzyme contains a large domain (catalytic domain or PLP- binding domain) and a small domain. The domains are joined by two peptide linkers (residues 32-35 and 138-146), with the internal gap created being the space for the active site[1] (Figure 1).
Two Dimers: Two monomers of hSDS (human SDH) come together to make a dimer. The interface between the two monomers is formed through hydrogen bonds and hydrophobic interactions. The monomer–monomer contacts involve six pairs of hydrogen bonds formed between 10 residues (Arg98-Asn260, Leu310-Asn260, and Leu265-Lys263). Additional interactions include a number of hydrophobic contacts between the residues Met17, Lys21, Asn101, Glu102, Ser306, Ile308, Ser309, and Ile264 in each monomer.[1] (Figure 2)
Cofactor Binding Site: The PLP cofactor is positioned in between the Beta-strands 7 and 10 of the large domain and lies on the large internal gap made between small and large domain. The cofactor is covalently bonded through a Schiff base linkage to Lys41. The cofactor is sandwiched between the side chain of Phe40 and the main chain of Ala222. Each of the polar substituents of PLP is coordinated by functional groups: the pyridinium nitrogen of PLP is hydrogen-bonded to the side chain of Cys303, the C3-hydroxyl group of PLP is hydrogen-bonded to the side chain of Asn67, and the phosphate group of PLP is coordinated by main chain amides from the tetraglycine loop.[1] (Figure 3 and Figure 4)
Enzyme Mechanism
Inhibitors
Biological Function
Disease Relevance
Evolution
Historical Significance
External links
- Serine+dehydratase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
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References
- ^ a b c d Lei, Sun (2005). "Crystal structure of the pyridoxal-5′-phosphate-dependent serine dehydratase from human liver" (PDF). Protein Science. 3. 14: 791–798. PMID PMC2279282. Retrieved 17 May 2011.
{{cite journal}}: Check|pmid=value (help); Unknown parameter|coauthors=ignored (|author=suggested) (help); Unknown parameter|month=ignored (help) - ^ "KEGG ENZYME Database Entry". Kyoto Encyclopedia of Genes and Genomes. Kanehisa Laboratories. Retrieved 17 May 2011.