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PDBsum entry 1a7a
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Hydrolase PDB id
1a7a

 

 

 

 

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Contents
Protein chain
431 a.a. *
Ligands
NAD ×2
ADC ×2
Waters ×46
* Residue conservation analysis
PDB id:
1a7a
Name: Hydrolase
Title: Structure of human placental s-adenosylhomocysteine hydrolase: determination of a 30 selenium atom substructure from data at a single wavelength
Structure: S-adenosylhomocysteine hydrolase. Chain: a, b. Engineered: yes. Other_details: selenomethionine derivatized protein
Source: Homo sapiens. Human. Organism_taxid: 9606. Tissue: placenta. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Homo-Tetramer (from PDB file)
Resolution:
2.80Å     R-factor:   0.227     R-free:   0.247
Authors: M.A.Turner,C.-S.Yuan,R.T.Borchardt,M.S.Hershfield,G.D.Smith, P.L.Howell
Key ref: M.A.Turner et al. (1998). Structure determination of selenomethionyl S-adenosylhomocysteine hydrolase using data at a single wavelength. Nat Struct Biol, 5, 369-376. PubMed id: 9586999
Date:
10-Mar-98     Release date:   20-Apr-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
P23526  (SAHH_HUMAN) -  Adenosylhomocysteinase from Homo sapiens
Seq:
Struc: 		432 a.a.
431 a.a.*
Key:    Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.3.13.2.1  - adenosylhomocysteinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: S-adenosyl-L-homocysteine + H2O = L-homocysteine + adenosine
S-adenosyl-L-homocysteine
 + H2O
 = L-homocysteine
 +
adenosine
Bound ligand (Het Group name = ADC)
matches with 89.47% similarity
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
Nat Struct Biol 5:369-376 (1998)
PubMed id: 9586999  
 
 
Structure determination of selenomethionyl S-adenosylhomocysteine hydrolase using data at a single wavelength.
M.A.Turner, C.S.Yuan, R.T.Borchardt, M.S.Hershfield, G.D.Smith, P.L.Howell.
 
  ABSTRACT  
 
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.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20693694 H.Xu (2010).
Enhancing MAD F(A) data for substructure determination.
  Acta Crystallogr D Biol Crystallogr, 66, 945-949.  
20179338 T.C.Terwilliger (2010).
Rapid model building of alpha-helices in electron-density maps.
  Acta Crystallogr D Biol Crystallogr, 66, 268-275.  
20179339 T.C.Terwilliger (2010).
Rapid model building of beta-sheets in electron-density maps.
  Acta Crystallogr D Biol Crystallogr, 66, 276-284.  
20179340 T.C.Terwilliger (2010).
Rapid chain tracing of polypeptide backbones in electron-density maps.
  Acta Crystallogr D Biol Crystallogr, 66, 285-294.  
19177456 O.Vugrek, R.Beluzić, N.Nakić, and S.H.Mudd (2009).
S-adenosylhomocysteine hydrolase (AHCY) deficiency: two novel mutations with lethal outcome.
  Hum Mutat, 30, E555-E565.  
19201949 R.P.Matthews, K.Lorent, R.Mañoral-Mobias, Y.Huang, W.Gong, I.V.Murray, I.A.Blair, and M.Pack (2009).
TNFalpha-dependent hepatic steatosis and liver degeneration caused by mutation of zebrafish S-adenosylhomocysteine hydrolase.
  Development, 136, 865-875.  
17932938 C.Hu, J.Fang, R.T.Borchardt, R.L.Schowen, and K.Kuczera (2008).
Molecular dynamics simulations of domain motions of substrate-free S-adenosyl- L-homocysteine hydrolase in solution.
  Proteins, 71, 131-143.  
18219117 H.Xu, and C.M.Weeks (2008).
Rapid and automated substructure solution by Shake-and-Bake.
  Acta Crystallogr D Biol Crystallogr, 64, 172-177.  
  18607106 K.Brzezinski, G.Bujacz, and M.Jaskolski (2008).
Purification, crystallization and preliminary crystallographic studies of plant S-adenosyl-L-homocysteine hydrolase (Lupinus luteus).
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 671-673.  
18815415 M.C.Reddy, G.Kuppan, N.D.Shetty, J.L.Owen, T.R.Ioerger, and J.C.Sacchettini (2008).
Crystal structures of Mycobacterium tuberculosis S-adenosyl-L-homocysteine hydrolase in ternary complex with substrate and inhibitors.
  Protein Sci, 17, 2134-2144.
PDB codes: 2ziz 2zj0 2zj1 3ce6 3dhy
18457953 S.F.Wnuk, P.R.Sacasa, E.Lewandowska, D.Andrei, S.Cai, and R.T.Borchardt (2008).
Synthesis of 5'-functionalized nucleosides: S-Adenosylhomocysteine analogues with the carbon-5' and sulfur atoms replaced by a vinyl or halovinyl unit.
  Bioorg Med Chem, 16, 5424-5433.  
17983264 C.H.Yeang, and D.Haussler (2007).
Detecting coevolution in and among protein domains.
  PLoS Comput Biol, 3, e211.  
17180248 J.O.Rosado, M.Salvador, and D.Bonatto (2007).
Importance of the trans-sulfuration pathway in cancer prevention and promotion.
  Mol Cell Biochem, 301, 1.  
17164794 K.Fumić, R.Beluzić, M.Cuk, T.Pavkov, D.Kloor, I.Barić, I.Mijić, and O.Vugrek (2007).
Functional analysis of human S-adenosylhomocysteine hydrolase isoforms SAHH-2 and SAHH-3.
  Eur J Hum Genet, 15, 347-351.  
17541248 M.Nakanishi (2007).
[S-adenosyl-L-homocysteine hydrolase as an attractive target for antimicrobial drugs]
  Yakugaku Zasshi, 127, 977-982.  
17048851 D.Andrei, and S.F.Wnuk (2006).
S-adenosylhomocysteine analogues with the carbon-5' and sulfur atoms replaced by a vinyl unit.
  Org Lett, 8, 5093-5096.  
16793548 H.Ando, A.Mizutani, H.Kiefer, D.Tsuzurugi, T.Michikawa, and K.Mikoshiba (2006).
IRBIT suppresses IP3 receptor activity by competing with IP3 for the common binding site on the IP3 receptor.
  Mol Cell, 22, 795-806.  
16951055 L.Mull, M.L.Ebbs, and J.Bender (2006).
A histone methylation-dependent DNA methylation pathway is uniquely impaired by deficiency in Arabidopsis S-adenosylhomocysteine hydrolase.
  Genetics, 174, 1161-1171.  
  16820692 N.G.Paterson, A.Riboldi-Tunnicliffe, T.J.Mitchell, and N.W.Isaacs (2006).
Purification, crystallization and preliminary X-ray diffraction analysis of RafE, a sugar-binding lipoprotein from Streptococcus pneumoniae.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 676-679.  
16929102 R.Pai, J.Sacchettini, and T.Ioerger (2006).
Identifying non-crystallographic symmetry in protein electron-density maps: a feature-based approach.
  Acta Crystallogr D Biol Crystallogr, 62, 1012-1021.  
15983421 H.Xu, C.M.Weeks, and H.A.Hauptman (2005).
Optimizing statistical Shake-and-Bake for Se-atom substructure determination.
  Acta Crystallogr D Biol Crystallogr, 61, 976-981.  
15645450 M.Porcelli, M.A.Moretti, L.Concilio, S.Forte, A.Merlino, G.Graziano, and G.Cacciapuoti (2005).
S-adenosylhomocysteine hydrolase from the archaeon Pyrococcus furiosus: biochemical characterization and analysis of protein structure by comparative molecular modeling.
  Proteins, 58, 815-825.  
16061414 T.Yamada, Y.Takata, J.Komoto, T.Gomi, H.Ogawa, M.Fujioka, and F.Takusagawa (2005).
Catalytic mechanism of S-adenosylhomocysteine hydrolase: roles of His 54, Asp130, Glu155, Lys185, and Aspl89.
  Int J Biochem Cell Biol, 37, 2417-2435.
PDB code: 1xwf
15044434 H.Teo, D.B.Veprintsev, and R.L.Williams (2004).
Structural insights into endosomal sorting complex required for transport (ESCRT-I) recognition of ubiquitinated proteins.
  J Biol Chem, 279, 28689-28696.
PDB code: 1uzx
14580338 B.Panic, O.Perisic, D.B.Veprintsev, R.L.Williams, and S.Munro (2003).
Structural basis for Arl1-dependent targeting of homodimeric GRIP domains to the Golgi apparatus.
  Mol Cell, 12, 863-874.
PDB code: 1upt
12525476 H.Ando, A.Mizutani, T.Matsu-ura, and K.Mikoshiba (2003).
IRBIT, a novel inositol 1,4,5-trisphosphate (IP3) receptor-binding protein, is released from the IP3 receptor upon IP3 binding to the receptor.
  J Biol Chem, 278, 10602-10612.  
12910461 J.M.Bujnicki, S.T.Prigge, D.Caridha, and P.K.Chiang (2003).
Structure, evolution, and inhibitor interaction of S-adenosyl-L-homocysteine hydrolase from Plasmodium falciparum.
  Proteins, 52, 624-632.  
12919315 R.K.Gordon, K.Ginalski, W.R.Rudnicki, L.Rychlewski, M.C.Pankaskie, J.M.Bujnicki, and P.K.Chiang (2003).
Anti-HIV-1 activity of 3-deaza-adenosine analogs. Inhibition of S-adenosylhomocysteine hydrolase and nucleotide congeners.
  Eur J Biochem, 270, 3507-3517.  
12429094 A.Stocker, T.Tomizaki, C.Schulze-Briese, and U.Baumann (2002).
Crystal structure of the human supernatant protein factor.
  Structure, 10, 1533-1540.
PDB code: 1o6u
11741948 Y.Huang, J.Komoto, Y.Takata, D.R.Powell, T.Gomi, H.Ogawa, M.Fujioka, and F.Takusagawa (2002).
Inhibition of S-adenosylhomocysteine hydrolase by acyclic sugar adenosine analogue D-eritadenine. Crystal structure of S-adenosylhomocysteine hydrolase complexed with D-eritadenine.
  J Biol Chem, 277, 7477-7482.
PDB code: 1k0u
10933798 D.Yin, X.Yang, Y.Hu, K.Kuczera, R.L.Schowen, R.T.Borchardt, and T.C.Squier (2000).
Substrate binding stabilizes S-adenosylhomocysteine hydrolase in a closed conformation.
  Biochemistry, 39, 9811-9818.  
11006535 S.E.Ealick (2000).
Advances in multiple wavelength anomalous diffraction crystallography.
  Curr Opin Chem Biol, 4, 495-499.  
11106503 X.Yang, D.Yin, S.F.Wnuk, M.J.Robins, and R.T.Borchardt (2000).
Mechanisms of inactivation of human S-adenosylhomocysteine hydrolase by 5',5',6',6'-tetradehydro-6'-deoxy-6'-halohomoadenosines.
  Biochemistry, 39, 15234-15241.  
10425674 A.M.Deacon, and S.E.Ealick (1999).
Selenium-based MAD phasing: setting the sites on larger structures.
  Structure, 7, R161-R166.  
10378277 J.L.Ekstrom, I.I.Mathews, B.A.Stanley, A.E.Pegg, and S.E.Ealick (1999).
The crystal structure of human S-adenosylmethionine decarboxylase at 2.25 A resolution reveals a novel fold.
  Structure, 7, 583-595.
PDB code: 1jen
10387078 Y.Hu, J.Komoto, Y.Huang, T.Gomi, H.Ogawa, Y.Takata, M.Fujioka, and F.Takusagawa (1999).
Crystal structure of S-adenosylhomocysteine hydrolase from rat liver.
  Biochemistry, 38, 8323-8333.
PDB code: 1b3r
10477256 Y.Xu, G.Bhargava, H.Wu, G.Loeber, and L.Tong (1999).
Crystal structure of human mitochondrial NAD(P)+-dependent malic enzyme: a new class of oxidative decarboxylases.
  Structure, 7, R877-R889.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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