1a7a

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STRUCTURE OF HUMAN PLACENTAL S-ADENOSYLHOMOCYSTEINE HYDROLASE: DETERMINATION OF A 30 SELENIUM ATOM SUBSTRUCTURE FROM DATA AT A SINGLE WAVELENGTH

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.
Method:X-ray diffraction, Resolution 2.8Å
Ligands:ADC, MSE, NAD
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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Citations
8 reviews cite this structure
Anomalous diffraction in crystallographic phase evaluation.
Hendrickson et al. (2014)
7 more
50 other articles
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See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ 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
  6. ↑ 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

Contents


PDB ID 1a7a

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