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PDBsum entry 1jbq

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protein ligands Protein-protein interface(s) links
Lyase PDB id
1jbq
Jmol
Contents
Protein chains
(+ 0 more) 348 a.a. *
Ligands
HEM ×6
PLP ×6
Waters ×154
* Residue conservation analysis
PDB id:
1jbq
Name: Lyase
Title: Structure of human cystathionine beta-synthase: a unique pyr phosphate dependent hemeprotein
Structure: Cystathionine beta-synthase. Chain: a, b, c, d, e, f. Fragment: the active core. Synonym: cystathionine-beta-synthase. Serine sulfhydrase. B thionase. Engineered: yes. Mutation: yes. Other_details: minor isoform
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
2.60Å     R-factor:   0.257     R-free:   0.296
Authors: M.Meier,M.Janosik,V.Kery,J.P.Kraus,P.Burkhard
Key ref:
M.Meier et al. (2001). Structure of human cystathionine beta-synthase: a unique pyridoxal 5'-phosphate-dependent heme protein. EMBO J, 20, 3910-3916. PubMed id: 11483494 DOI: 10.1093/emboj/20.15.3910
Date:
06-Jun-01     Release date:   12-Aug-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P35520  (CBS_HUMAN) -  Cystathionine beta-synthase
Seq:
Struc:
 
Seq:
Struc:
551 a.a.
348 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.4.2.1.22  - Cystathionine beta-synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: L-serine + L-homocysteine = L-cystathionine + H2O
L-serine
+ L-homocysteine
= L-cystathionine
+ H(2)O
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
Bound ligand (Het Group name = PLP) matches with 93.75% similarity
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     cysteine biosynthetic process from serine   2 terms 
  Biochemical function     cystathionine beta-synthase activity     1 term  

 

 
    reference    
 
 
DOI no: 10.1093/emboj/20.15.3910 EMBO J 20:3910-3916 (2001)
PubMed id: 11483494  
 
 
Structure of human cystathionine beta-synthase: a unique pyridoxal 5'-phosphate-dependent heme protein.
M.Meier, M.Janosik, V.Kery, J.P.Kraus, P.Burkhard.
 
  ABSTRACT  
 
Cystathionine beta-synthase (CBS) is a unique heme- containing enzyme that catalyzes a pyridoxal 5'-phosphate (PLP)-dependent condensation of serine and homocysteine to give cystathionine. Deficiency of CBS leads to homocystinuria, an inherited disease of sulfur metabolism characterized by increased levels of the toxic metabolite homocysteine. Here we present the X-ray crystal structure of a truncated form of the enzyme. CBS shares the same fold with O-acetylserine sulfhydrylase but it contains an additional N-terminal heme binding site. This heme binding motif together with a spatially adjacent oxidoreductase active site motif could explain the regulation of its enzyme activity by redox changes.
 
  Selected figure(s)  
 
Figure 1.
Figure 1 Transsulfuration pathway.
Figure 3.
Figure 3 Structural details of CBS. (A) The active site region of CBS (gray) in a superposition with the active site of OASS (green). The sequences as well as the structure of the two enzymes are very similar. A superposition of the 25 structurally most conserved residues yields an r.m.s.d. of 1.6 of their C[ ]positions. The substrate analog of OASS methionine indicates the probable binding mode of the first substrate serine and also the region where the second substrate homocysteine is expected to bind. (B) The heme binding site of CBS with heme in green and the surrounding residues in gray. The two residues His65 and Cys52 are the ligands to the heme iron (dark red). The difference density for the cofactor is shown in red contoured at 3.5 . (C) The oxidoreductase motif in ball-and-stick representation and (D) in a superposition with the structure of glutaredoxin. The structure of CBS is in gray, the one of glutaredoxin in green. The overall topology is very similar, but the active site motif in CBS is switched to the other helix compared with glutaredoxin.
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2001, 20, 3910-3916) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21460844 B.P.Callahan, N.I.Topilina, M.J.Stanger, P.Van Roey, and M.Belfort (2011).
Structure of catalytically competent intein caught in a redox trap with functional and evolutionary implications.
  Nat Struct Mol Biol, 18, 630-633.
PDB code: 3nzm
20490928 J.Kopecká, J.Krijt, K.Raková, and V.Kožich (2011).
Restoring assembly and activity of cystathionine β-synthase mutants by ligands and chemical chaperones.
  J Inherit Metab Dis, 34, 39-48.  
21308989 S.H.Mudd (2011).
Hypermethioninemias of genetic and non-genetic origin: A review.
  Am J Med Genet C Semin Med Genet, 157, 3.  
19769466 D.R.Linden, M.D.Levitt, G.Farrugia, and J.H.Szurszewski (2010).
Endogenous production of H2S in the gastrointestinal tract: still in search of a physiologic function.
  Antioxid Redox Signal, 12, 1135-1146.  
20544970 L.J.Smith, A.Kahraman, and J.M.Thornton (2010).
Heme proteins--diversity in structural characteristics, function, and folding.
  Proteins, 78, 2349-2368.  
20066033 L.R.Singh, S.Gupta, N.H.Honig, J.P.Kraus, and W.D.Kruger (2010).
Activation of mutant enzyme function in vivo by proteasome inhibitors and treatments that induce Hsp70.
  PLoS Genet, 6, e1000807.  
19939208 M.Kajimura, R.Fukuda, R.M.Bateman, T.Yamamoto, and M.Suematsu (2010).
Interactions of multiple gas-transducing systems: hallmarks and uncertainties of CO, NO, and H2S gas biology.
  Antioxid Redox Signal, 13, 157-192.  
21081698 M.Koutmos, O.Kabil, J.L.Smith, and R.Banerjee (2010).
Structural basis for substrate activation and regulation by cystathionine beta-synthase (CBS) domains in cystathionine {beta}-synthase.
  Proc Natl Acad Sci U S A, 107, 20958-20963.
PDB codes: 3pc2 3pc3 3pc4
20155941 V.Karunakaran, A.Benabbas, Y.Sun, Z.Zhang, S.Singh, R.Banerjee, and P.M.Champion (2010).
Investigations of low-frequency vibrational dynamics and ligand binding kinetics of cystathionine beta-synthase.
  J Phys Chem B, 114, 3294-3306.  
20506325 V.Kozich, J.Sokolová, V.Klatovská, J.Krijt, M.Janosík, K.Jelínek, and J.P.Kraus (2010).
Cystathionine beta-synthase mutations: effect of mutation topology on folding and activity.
  Hum Mutat, 31, 809-819.  
19760175 C.A.Opere, E.M.Monjok, K.H.Kulkarni, Y.F.Njie, and S.E.Ohia (2009).
Regulation of [(3)h] d: -aspartate release from mammalian isolated retinae by hydrogen sulfide.
  Neurochem Res, 34, 1962-1968.  
19722721 C.L.Weeks, S.Singh, P.Madzelan, R.Banerjee, and T.G.Spiro (2009).
Heme regulation of human cystathionine beta-synthase activity: insights from fluorescence and Raman spectroscopy.
  J Am Chem Soc, 131, 12809-12816.  
18629636 K.H.Kulkarni, E.M.Monjok, R.Zeyssig, G.Kouamou, O.N.Bongmba, C.A.Opere, Y.F.Njie, and S.E.Ohia (2009).
Effect of hydrogen sulfide on sympathetic neurotransmission and catecholamine levels in isolated porcine iris-ciliary body.
  Neurochem Res, 34, 400-406.  
19733148 L.Celano, M.Gil, S.Carballal, R.Durán, A.Denicola, R.Banerjee, and B.Alvarez (2009).
Inactivation of cystathionine beta-synthase with peroxynitrite.
  Arch Biochem Biophys, 491, 96.  
19074437 L.R.Singh, and W.D.Kruger (2009).
Functional Rescue of Mutant Human Cystathionine {beta}-Synthase by Manipulation of Hsp26 and Hsp70 Levels in Saccharomyces cerevisiae.
  J Biol Chem, 284, 4238-4245.  
19685245 M.Sieńko, R.Natorff, S.Owczarek, I.Olewiecki, and A.Paszewski (2009).
Aspergillus nidulans genes encoding reverse transsulfuration enzymes belong to homocysteine regulon.
  Curr Genet, 55, 561-570.  
19448746 P.H.Lodha, H.Shadnia, C.M.Woodhouse, J.S.Wright, and S.M.Aitken (2009).
Investigation of residues Lys112, Glu136, His138, Gly247, Tyr248, and Asp249 in the active site of yeast cystathionine beta-synthase.
  Biochem Cell Biol, 87, 531-540.  
19888216 Q.Zhong, N.Simonis, Q.R.Li, B.Charloteaux, F.Heuze, N.Klitgord, S.Tam, H.Yu, K.Venkatesan, D.Mou, V.Swearingen, M.A.Yildirim, H.Yan, A.Dricot, D.Szeto, C.Lin, T.Hao, C.Fan, S.Milstein, D.Dupuy, R.Brasseur, D.E.Hill, M.E.Cusick, and M.Vidal (2009).
Edgetic perturbation models of human inherited disorders.
  Mol Syst Biol, 5, 321.  
19296828 R.A.Williams, G.D.Westrop, and G.H.Coombs (2009).
Two pathways for cysteine biosynthesis in Leishmania major.
  Biochem J, 420, 451-462.  
19232736 S.Singh, P.Madzelan, J.Stasser, C.L.Weeks, D.Becker, T.G.Spiro, J.Penner-Hahn, and R.Banerjee (2009).
Modulation of the heme electronic structure and cystathionine beta-synthase activity by second coordination sphere ligands: The role of heme ligand switching in redox regulation.
  J Inorg Biochem, 103, 689-697.  
19085910 T.Shintani, T.Iwabuchi, T.Soga, Y.Kato, T.Yamamoto, N.Takano, T.Hishiki, Y.Ueno, S.Ikeda, T.Sakuragawa, K.Ishikawa, N.Goda, Y.Kitagawa, M.Kajimura, K.Matsumoto, and M.Suematsu (2009).
Cystathionine beta-synthase as a carbon monoxide-sensitive regulator of bile excretion.
  Hepatology, 49, 141-150.  
17334902 M.A.Grillo, and S.Colombatto (2008).
S-adenosylmethionine and its products.
  Amino Acids, 34, 187-193.  
18021800 M.Proudfoot, S.A.Sanders, A.Singer, R.Zhang, G.Brown, A.Binkowski, L.Xu, J.A.Lukin, A.G.Murzin, A.Joachimiak, C.H.Arrowsmith, A.M.Edwards, A.V.Savchenko, and A.F.Yakunin (2008).
Biochemical and structural characterization of a novel family of cystathionine beta-synthase domain proteins fused to a Zn ribbon-like domain.
  J Mol Biol, 375, 301-315.
PDB codes: 1pvm 2qh1
18849566 T.Majtan, L.R.Singh, L.Wang, W.D.Kruger, and J.P.Kraus (2008).
Active Cystathionine {beta}-Synthase Can Be Expressed in Heme-free Systems in the Presence of Metal-substituted Porphyrins or a Chemical Chaperone.
  J Biol Chem, 283, 34588-34595.  
18641671 V.Brancaleone, F.Roviezzo, V.Vellecco, L.De Gruttola, M.Bucci, and G.Cirino (2008).
Biosynthesis of H2S is impaired in non-obese diabetic (NOD) mice.
  Br J Pharmacol, 155, 673-680.  
17077084 H.M.Girvan, H.E.Seward, H.S.Toogood, M.R.Cheesman, D.Leys, and A.W.Munro (2007).
Structural and spectroscopic characterization of P450 BM3 mutants with unprecedented P450 heme iron ligand sets. New heme ligation states influence conformational equilibria in P450 BM3.
  J Biol Chem, 282, 564-572.
PDB codes: 2ij2 2ij3 2ij4
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.  
17540596 L.R.Singh, X.Chen, V.Kozich, and W.D.Kruger (2007).
Chemical chaperone rescue of mutant human cystathionine beta-synthase.
  Mol Genet Metab, 91, 335-342.  
17534535 S.Singh, P.Madzelan, and R.Banerjee (2007).
Properties of an unusual heme cofactor in PLP-dependent cystathionine beta-synthase.
  Nat Prod Rep, 24, 631-639.  
16328106 D.Johansen, K.Ytrehus, and G.F.Baxter (2006).
Exogenous hydrogen sulfide (H2S) protects against regional myocardial ischemia-reperfusion injury--Evidence for a role of K ATP channels.
  Basic Res Cardiol, 101, 53-60.  
17046821 D.K.Simanshu, H.S.Savithri, and M.R.Murthy (2006).
Crystal structures of Salmonella typhimurium biodegradative threonine deaminase and its complex with CMP provide structural insights into ligand-induced oligomerization and enzyme activation.
  J Biol Chem, 281, 39630-39641.
PDB codes: 2gn0 2gn1 2gn2
16831608 S.Fiorucci, E.Distrutti, G.Cirino, and J.L.Wallace (2006).
The emerging roles of hydrogen sulfide in the gastrointestinal tract and liver.
  Gastroenterology, 131, 259-271.  
15890000 C.G.Zou, and R.Banerjee (2005).
Homocysteine and redox signaling.
  Antioxid Redox Signal, 7, 547-559.  
  15626644 J.H.Schafer, T.A.Glass, J.Bressler, A.C.Todd, and B.S.Schwartz (2005).
Blood lead is a predictor of homocysteine levels in a population-based study of older adults.
  Environ Health Perspect, 113, 31-35.  
15890029 K.H.Jhee, and W.D.Kruger (2005).
The role of cystathionine beta-synthase in homocysteine metabolism.
  Antioxid Redox Signal, 7, 813-822.  
15087459 E.W.Miles, and J.P.Kraus (2004).
Cystathionine beta-synthase: structure, function, regulation, and location of homocystinuria-causing mutations.
  J Biol Chem, 279, 29871-29874.  
15189131 M.H.Stipanuk (2004).
Sulfur amino acid metabolism: pathways for production and removal of homocysteine and cysteine.
  Annu Rev Nutr, 24, 539-577.  
14962267 S.Pavlovic, M.Kuzmanovic, J.Urosevic, J.Poznanic, T.Zoranovic, V.Djordjevic, N.Rasovic, G.Bunjevacki, M.Cvorkov-Drazic, and M.Colovic (2004).
Severe central nervous system thrombotic events in hemoglobin Sabine patient.
  Eur J Haematol, 72, 67-70.  
12615917 C.G.Zou, and R.Banerjee (2003).
Tumor necrosis factor-alpha-induced targeted proteolysis of cystathionine beta-synthase modulates redox homeostasis.
  J Biol Chem, 278, 16802-16808.  
12644499 K.Mino, and K.Ishikawa (2003).
Characterization of a novel thermostable O-acetylserine sulfhydrylase from Aeropyrum pernix K1.
  J Bacteriol, 185, 2277-2284.  
12554945 K.Mino, Y.Oda, M.Ataka, and K.Ishikawa (2003).
Crystallization and preliminary X-ray diffraction analysis of O-acetylserine sulfhydrylase from Aeropyrum pernix K1.
  Acta Crystallogr D Biol Crystallogr, 59, 338-340.  
12952961 R.Omi, M.Goto, I.Miyahara, H.Mizuguchi, H.Hayashi, H.Kagamiyama, and K.Hirotsu (2003).
Crystal structures of threonine synthase from Thermus thermophilus HB8: conformational change, substrate recognition, and mechanism.
  J Biol Chem, 278, 46035-46045.
PDB codes: 1uim 1uin 1uiq 1v7c
12882962 T.Ose, A.Fujino, M.Yao, N.Watanabe, M.Honma, and I.Tanaka (2003).
Reaction intermediate structures of 1-aminocyclopropane-1-carboxylate deaminase: insight into PLP-dependent cyclopropane ring-opening reaction.
  J Biol Chem, 278, 41069-41076.
PDB codes: 1j0c 1j0d 1j0e
14596599 T.Yamada, J.Komoto, Y.Takata, H.Ogawa, H.C.Pitot, and F.Takusagawa (2003).
Crystal structure of serine dehydratase from rat liver.
  Biochemistry, 42, 12854-12865.
PDB codes: 1pwe 1pwh
11790955 B.Deplancke, and H.R.Gaskins (2002).
Redox control of the transsulfuration and glutathione biosynthesis pathways.
  Curr Opin Clin Nutr Metab Care, 5, 85-92.  
12379655 J.Oliveriusová, V.Kery, K.N.Maclean, and J.P.Kraus (2002).
Deletion mutagenesis of human cystathionine beta-synthase. Impact on activity, oligomeric status, and S-adenosylmethionine regulation.
  J Biol Chem, 277, 48386-48394.  
12124992 M.Gaustadnes, B.Wilcken, J.Oliveriusova, J.McGill, J.Fletcher, J.P.Kraus, and D.E.Wilcken (2002).
The molecular basis of cystathionine beta-synthase deficiency in Australian patients: genotype-phenotype correlations and response to treatment.
  Hum Mutat, 20, 117-126.  
12455965 S.C.Lo, L.Hamer, and J.E.Hamer (2002).
Molecular characterization of a cystathionine beta-synthase gene, CBS1, in Magnaporthe grisea.
  Eukaryot Cell, 1, 311-314.  
11948191 S.Taoka, and R.Banerjee (2002).
Stopped-flow kinetic analysis of the reaction catalyzed by the full-length yeast cystathionine beta-synthase.
  J Biol Chem, 277, 22421-22425.  
12411478 V.A.Bamford, S.Bruno, T.Rasmussen, C.Appia-Ayme, M.R.Cheesman, B.C.Berks, and A.M.Hemmings (2002).
Structural basis for the oxidation of thiosulfate by a sulfur cycle enzyme.
  EMBO J, 21, 5599-5610.
PDB codes: 1h31 1h32 1h33
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 code is shown on the right.