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| - | {{STRUCTURE_1a7a| PDB=1a7a | SCENE= }}
| + | ==STRUCTURE OF HUMAN PLACENTAL S-ADENOSYLHOMOCYSTEINE HYDROLASE: DETERMINATION OF A 30 SELENIUM ATOM SUBSTRUCTURE FROM DATA AT A SINGLE WAVELENGTH== |
| - | ===STRUCTURE OF HUMAN PLACENTAL S-ADENOSYLHOMOCYSTEINE HYDROLASE: DETERMINATION OF A 30 SELENIUM ATOM SUBSTRUCTURE FROM DATA AT A SINGLE WAVELENGTH===
| + | <StructureSection load='1a7a' size='340' side='right' caption='[[1a7a]], [[Resolution|resolution]] 2.80Å' scene=''> |
| - | {{ABSTRACT_PUBMED_9586999}}
| + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1a7a]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A7A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1A7A FirstGlance]. <br> |
| | + | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADC:(1R,2S)-9-(2-HYDROXY-3-KETO-CYCLOPENTEN-1-YL)ADENINE'>ADC</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene><br> |
| | + | <tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| | + | <tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenosylhomocysteinase Adenosylhomocysteinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.3.1.1 3.3.1.1] </span></td></tr> |
| | + | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1a7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a7a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1a7a RCSB], [http://www.ebi.ac.uk/pdbsum/1a7a PDBsum]</span></td></tr> |
| | + | <table> |
| | + | == Disease == |
| | + | [[http://www.uniprot.org/uniprot/SAHH_HUMAN SAHH_HUMAN]] Defects in AHCY are the cause of hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency (HMAHCHD) [MIM:[http://omim.org/entry/613752 613752]]. A metabolic disorder characterized by hypermethioninemia associated with failure to thrive, mental and motor retardation, facial dysmorphism with abnormal hair and teeth, and myocardiopathy.<ref>PMID:15024124</ref> <ref>PMID:16736098</ref> <ref>PMID:19177456</ref> <ref>PMID:20852937</ref> |
| | + | == Function == |
| | + | [[http://www.uniprot.org/uniprot/SAHH_HUMAN SAHH_HUMAN]] Adenosylhomocysteine is a competitive inhibitor of S-adenosyl-L-methionine-dependent methyl transferase reactions; therefore adenosylhomocysteinase may play a key role in the control of methylations via regulation of the intracellular concentration of adenosylhomocysteine.<ref>PMID:12590576</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a7/1a7a_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | S-Adenosylhomocysteine (AdoHcy) hydrolase regulates all adenosylmethionine-(AdoMet) dependent transmethylations by hydrolyzing the potent feedback inhibitor AdoHcy to homocysteine and adenosine. The crystallographic structure determination of a selenomethionyl-incorporated AdoHcy hydrolase inhibitor complex was accomplished using single wavelength anomalous diffraction data and the direct methods program, Snb v2.0, which produced the positions of all 30 crystallographically distinct selenium atoms. The mode of enzyme-cofactor binding is unique, requiring interactions from two protein monomers. An unusual dual role for a catalytic water molecule in the active site is revealed in the complex with the adenosine analog 2'-hydroxy, 3'-ketocyclopent-4'-enyladenine. |
| | | | |
| - | ==Disease==
| + | Structure determination of selenomethionyl S-adenosylhomocysteine hydrolase using data at a single wavelength.,Turner MA, Yuan CS, Borchardt RT, Hershfield MS, Smith GD, Howell PL Nat Struct Biol. 1998 May;5(5):369-76. PMID:9586999<ref>PMID:9586999</ref> |
| - | [[http://www.uniprot.org/uniprot/SAHH_HUMAN SAHH_HUMAN]] Defects in AHCY are the cause of hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency (HMAHCHD) [MIM:[http://omim.org/entry/613752 613752]]. A metabolic disorder characterized by hypermethioninemia associated with failure to thrive, mental and motor retardation, facial dysmorphism with abnormal hair and teeth, and myocardiopathy.<ref>PMID:15024124</ref><ref>PMID:16736098</ref><ref>PMID:19177456</ref><ref>PMID:20852937</ref>
| + | |
| | | | |
| - | ==Function==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | [[http://www.uniprot.org/uniprot/SAHH_HUMAN SAHH_HUMAN]] Adenosylhomocysteine is a competitive inhibitor of S-adenosyl-L-methionine-dependent methyl transferase reactions; therefore adenosylhomocysteinase may play a key role in the control of methylations via regulation of the intracellular concentration of adenosylhomocysteine.<ref>PMID:12590576</ref>
| + | </div> |
| | | | |
| - | ==About this Structure== | + | ==See Also== |
| - | [[1a7a]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A7A OCA]. | + | *[[S-adenosylhomocysteine hydrolase|S-adenosylhomocysteine hydrolase]] |
| - | | + | == References == |
| - | ==Reference== | + | <references/> |
| - | <ref group="xtra">PMID:009586999</ref><ref group="xtra">PMID:011178916</ref><references group="xtra"/><references/>
| + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Adenosylhomocysteinase]] | | [[Category: Adenosylhomocysteinase]] |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| Structural highlights
1a7a is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | ,
| | NonStd Res: | |
| Activity: | Adenosylhomocysteinase, with EC number 3.3.1.1 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[SAHH_HUMAN] Defects in AHCY are the cause of hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency (HMAHCHD) [MIM:613752]. A metabolic disorder characterized by hypermethioninemia associated with failure to thrive, mental and motor retardation, facial dysmorphism with abnormal hair and teeth, and myocardiopathy.[1] [2] [3] [4]
Function
[SAHH_HUMAN] Adenosylhomocysteine is a competitive inhibitor of S-adenosyl-L-methionine-dependent methyl transferase reactions; therefore adenosylhomocysteinase may play a key role in the control of methylations via regulation of the intracellular concentration of adenosylhomocysteine.[5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
S-Adenosylhomocysteine (AdoHcy) hydrolase regulates all adenosylmethionine-(AdoMet) dependent transmethylations by hydrolyzing the potent feedback inhibitor AdoHcy to homocysteine and adenosine. The crystallographic structure determination of a selenomethionyl-incorporated AdoHcy hydrolase inhibitor complex was accomplished using single wavelength anomalous diffraction data and the direct methods program, Snb v2.0, which produced the positions of all 30 crystallographically distinct selenium atoms. The mode of enzyme-cofactor binding is unique, requiring interactions from two protein monomers. An unusual dual role for a catalytic water molecule in the active site is revealed in the complex with the adenosine analog 2'-hydroxy, 3'-ketocyclopent-4'-enyladenine.
Structure determination of selenomethionyl S-adenosylhomocysteine hydrolase using data at a single wavelength.,Turner MA, Yuan CS, Borchardt RT, Hershfield MS, Smith GD, Howell PL Nat Struct Biol. 1998 May;5(5):369-76. PMID:9586999[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Baric I, Fumic K, Glenn B, Cuk M, Schulze A, Finkelstein JD, James SJ, Mejaski-Bosnjak V, Pazanin L, Pogribny IP, Rados M, Sarnavka V, Scukanec-Spoljar M, Allen RH, Stabler S, Uzelac L, Vugrek O, Wagner C, Zeisel S, Mudd SH. S-adenosylhomocysteine hydrolase deficiency in a human: a genetic disorder of methionine metabolism. Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4234-9. Epub 2004 Mar 15. PMID:15024124 doi:10.1073/pnas.0400658101
- ↑ Buist NR, Glenn B, Vugrek O, Wagner C, Stabler S, Allen RH, Pogribny I, Schulze A, Zeisel SH, Baric I, Mudd SH. S-adenosylhomocysteine hydrolase deficiency in a 26-year-old man. J Inherit Metab Dis. 2006 Aug;29(4):538-45. Epub 2006 May 30. PMID:16736098 doi:10.1007/s10545-006-0240-0
- ↑ Vugrek O, Beluzic R, Nakic N, Mudd SH. S-adenosylhomocysteine hydrolase (AHCY) deficiency: two novel mutations with lethal outcome. Hum Mutat. 2009 Apr;30(4):E555-65. doi: 10.1002/humu.20985. PMID:19177456 doi:10.1002/humu.20985
- ↑ Grubbs R, Vugrek O, Deisch J, Wagner C, Stabler S, Allen R, Baric I, Rados M, Mudd SH. S-adenosylhomocysteine hydrolase deficiency: two siblings with fetal hydrops and fatal outcomes. J Inherit Metab Dis. 2010 Dec;33(6):705-13. doi: 10.1007/s10545-010-9171-x. Epub , 2010 Sep 18. PMID:20852937 doi:10.1007/s10545-010-9171-x
- ↑ Yang X, Hu Y, Yin DH, Turner MA, Wang M, Borchardt RT, Howell PL, Kuczera K, Schowen RL. Catalytic strategy of S-adenosyl-L-homocysteine hydrolase: transition-state stabilization and the avoidance of abortive reactions. Biochemistry. 2003 Feb 25;42(7):1900-9. PMID:12590576 doi:http://dx.doi.org/10.1021/bi0262350
- ↑ Turner MA, Yuan CS, Borchardt RT, Hershfield MS, Smith GD, Howell PL. Structure determination of selenomethionyl S-adenosylhomocysteine hydrolase using data at a single wavelength. Nat Struct Biol. 1998 May;5(5):369-76. PMID:9586999
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