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PDBsum entry 1awm
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protein ligands metals Protein-protein interface(s) links
Lyase PDB id
1awm

 

 

 

 

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Contents
Protein chains
157 a.a.
Ligands
ATP ×2
Metals
_MG ×2
Theoretical model
PDB id:
1awm
Name: Lyase
Title: Theoretical model of the germination specific adenylyl cyclase
Structure: Germination specific adenylyl cyclase. Chain: a, b. Biological_unit: homodimer
Source: Dictyostelium discoideum. Slime mold
Authors: J.H.Hurley,V.D.Rao
Key ref:
Y.Liu et al. (1997). Catalytic mechanism of the adenylyl and guanylyl cyclases: modeling and mutational analysis. Proc Natl Acad Sci U S A, 94, 13414-13419. PubMed id: 9391039 DOI: 10.1073/pnas.94.25.13414
Date:
03-Oct-97     Release date:   28-Jan-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q03101  (CYAG_DICDI) -  Adenylate cyclase, germination specific from Dictyostelium discoideum
Seq:
Struc: 		 
Seq:
Struc: 		858 a.a.
157 a.a.
Key:    PfamA domain  Secondary structure

 

 
DOI no: 10.1073/pnas.94.25.13414 Proc Natl Acad Sci U S A 94:13414-13419 (1997)
PubMed id: 9391039  
 
 
Catalytic mechanism of the adenylyl and guanylyl cyclases: modeling and mutational analysis.
Y.Liu, A.E.Ruoho, V.D.Rao, J.H.Hurley.
 
  ABSTRACT  
 
The adenylyl and guanylyl cyclases catalyze the formation of 3', 5'-cyclic adenosine or guanosine monophosphate from the corresponding nucleoside 5'-triphosphate. The guanylyl cyclases, the mammalian adenylyl cyclases, and their microbial homologues function as pairs of homologous catalytic domains. The crystal structure of the rat type II adenylyl cyclase C2 catalytic domain was used to model by homology a mammalian adenylyl cyclase C1-C2 domain pair, a homodimeric adenylyl cyclase of Dictyostelium discoideum, a heterodimeric soluble guanylyl cyclase, and a homodimeric membrane guanylyl cyclase. Mg2+ATP or Mg2+GTP were docked into the active sites based on known stereochemical constraints on their conformation. The models are consistent with the activities of seven active-site mutants. Asp-310 and Glu-432 of type I adenylyl cyclase coordinate a Mg2+ ion. The D310S and D310A mutants have 10-fold reduced Vmax and dependence. The NTP purine moieties bind in mostly hydrophobic pockets. Specificity is conferred by a Lys and an Asp in adenylyl cyclase, and a Glu, an Arg, and a Cys in guanylyl cyclase. The models predict that an Asp from one domain is a general base in the reaction, and that the transition state is stabilized by a conserved Asn-Arg pair on the other domain.
 
  Selected figure(s)  
 
Figure 2.
Fig. 2. Sequence alignment colored by residue function. Based on modeling, catalytic, Me^2+, pyrophosphate ligands are red; forskolin, magenta; adenine, dark green; and guanine, gold. The Gs binding site is gray (20), and G is blue (21). Dimer interface: blue underscores; h, hydrophobic pocket. The C-terminal 60 aa are omitted. 		Figure 7.
Fig. 7. Hypothetical reaction mechanism, using AC1 as an example.
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21375691 K.N.Pandey (2011).
The functional genomics of guanylyl cyclase/natriuretic peptide receptor-A: Perspectives and paradigms.
  FEBS J, 278, 1792-1807.  
  21375693 K.S.Misono, J.S.Philo, T.Arakawa, C.M.Ogata, Y.Qiu, H.Ogawa, and H.S.Young (2011).
Structure, signaling mechanism and regulation of the natriuretic peptide receptor guanylate cyclase.
  FEBS J, 278, 1818-1829.  
20579354 C.Gehring (2010).
Adenyl cyclases and cAMP in plant signaling - past and present.
  Cell Commun Signal, 8, 15.  
20517349 S.A.Ugur Iseri, Y.K.Durlu, and A.Tolun (2010).
A novel recessive GUCY2D mutation causing cone-rod dystrophy and not Leber's congenital amaurosis.
  Eur J Hum Genet, 18, 1121-1126.  
20126659 S.Meier, O.Ruzvidzo, M.Morse, L.Donaldson, L.Kwezi, and C.Gehring (2010).
The Arabidopsis wall associated kinase-like 10 gene encodes a functional guanylyl cyclase and is co-expressed with pathogen defense related genes.
  PLoS One, 5, e8904.  
19638320 B.Pavan, C.Biondi, and A.Dalpiaz (2009).
Adenylyl cyclases as innovative therapeutic goals.
  Drug Discov Today, 14, 982-991.  
19648115 S.Saha, K.H.Biswas, C.Kondapalli, N.Isloor, and S.S.Visweswariah (2009).
The linker region in receptor guanylyl cyclases is a key regulatory module: mutational analysis of guanylyl cyclase C.
  J Biol Chem, 284, 27135-27145.  
19137266 T.Duda, S.Bharill, I.Wojtas, P.Yadav, I.Gryczynski, Z.Gryczynski, and R.K.Sharma (2009).
Atrial natriuretic factor receptor guanylate cyclase signaling: new ATP-regulated transduction motif.
  Mol Cell Biochem, 324, 39-53.  
18632300 A.I.den Hollander, R.Roepman, R.K.Koenekoop, and F.P.Cremers (2008).
Leber congenital amaurosis: genes, proteins and disease mechanisms.
  Prog Retin Eye Res, 27, 391-419.  
18840690 A.Rauch, M.Leipelt, M.Russwurm, and C.Steegborn (2008).
Crystal structure of the guanylyl cyclase Cya2.
  Proc Natl Acad Sci U S A, 105, 15720-15725.
PDB code: 2w01
17680656 B.K.Cho, H.Y.Park, J.H.Seo, J.Kim, T.J.Kang, B.S.Lee, and B.G.Kim (2008).
Redesigning the substrate specificity of omega-aminotransferase for the kinetic resolution of aliphatic chiral amines.
  Biotechnol Bioeng, 99, 275-284.  
18087651 F.Dimitriadis, D.Giannakis, N.Pardalidis, K.Zikopoulos, E.Paraskevaidis, N.Giotitsas, V.Kalaboki, P.Tsounapi, D.Baltogiannis, I.Georgiou, M.Saito, T.Watanabe, I.Miyagawa, and N.Sofikitis (2008).
Effects of phosphodiesterase-5 inhibitors on sperm parameters and fertilizing capacity.
  Asian J Androl, 10, 115-133.  
18842118 J.A.Winger, E.R.Derbyshire, M.H.Lamers, M.A.Marletta, and J.Kuriyan (2008).
The crystal structure of the catalytic domain of a eukaryotic guanylate cyclase.
  BMC Struct Biol, 8, 42.
PDB code: 3et6
18500817 V.Venkataraman, T.Duda, S.Ravichandran, and R.K.Sharma (2008).
Neurocalcin delta modulation of ROS-GC1, a new model of Ca(2+) signaling.
  Biochemistry, 47, 6590-6601.  
18515359 X.Hu, L.B.Murata, A.Weichsel, J.L.Brailey, S.A.Roberts, A.Nighorn, and W.R.Montfort (2008).
Allostery in recombinant soluble guanylyl cyclase from Manduca sexta.
  J Biol Chem, 283, 20968-20977.  
  19122779 D.B.Morton, and A.Vermehren (2007).
Soluble Guanylyl Cyclases in Invertebrates: Targets for NO and O(2).
  Adv Exp Biol, 1, 65-82.  
17520012 L.Kwezi, S.Meier, L.Mungur, O.Ruzvidzo, H.Irving, and C.Gehring (2007).
The Arabidopsis thaliana brassinosteroid receptor (AtBRI1) contains a domain that functions as a guanylyl cyclase in vitro.
  PLoS ONE, 2, e449.  
  19704552 S.Meier, C.Seoighe, L.Kwezi, H.Irving, and C.Gehring (2007).
Plant nucleotide cyclases: an increasingly complex and growing family.
  Plant Signal Behav, 2, 536-539.  
15955067 L.I.Castro, C.Hermsen, J.E.Schultz, and J.U.Linder (2005).
Adenylyl cyclase Rv0386 from Mycobacterium tuberculosis H37Rv uses a novel mode for substrate selection.
  FEBS J, 272, 3085-3092.  
14747729 A.D.Ketkar, A.R.Shenoy, M.M.Kesavulu, S.S.Visweswariah, and K.Suguna (2004).
Purification, crystallization and preliminary X-ray diffraction analysis of the catalytic domain of adenylyl cyclase Rv1625c from Mycobacterium tuberculosis.
  Acta Crystallogr D Biol Crystallogr, 60, 371-373.  
15203005 B.H.Cheung, F.Arellano-Carbajal, I.Rybicki, and M.de Bono (2004).
Soluble guanylate cyclases act in neurons exposed to the body fluid to promote C. elegans aggregation behavior.
  Curr Biol, 14, 1105-1111.  
15165228 D.A.Baker, and J.M.Kelly (2004).
Structure, function and evolution of microbial adenylyl and guanylyl cyclases.
  Mol Microbiol, 52, 1229-1242.  
15326296 P.Pellicena, D.S.Karow, E.M.Boon, M.A.Marletta, and J.Kuriyan (2004).
Crystal structure of an oxygen-binding heme domain related to soluble guanylate cyclases.
  Proc Natl Acad Sci U S A, 101, 12854-12859.
PDB codes: 1u4h 1u55 1u56
14718564 S.Saran, and P.Schaap (2004).
Adenylyl cyclase G is activated by an intramolecular osmosensor.
  Mol Biol Cell, 15, 1479-1486.  
12558998 D.B.Morton, and A.Nighorn (2003).
MsGC-II, a receptor guanylyl cyclase isolated from the CNS of Manduca sexta that is inhibited by calcium.
  J Neurochem, 84, 363-372.  
  12019229 C.Moorman, and R.H.Plasterk (2002).
Functional characterization of the adenylyl cyclase gene sgs-1 by analysis of a mutational spectrum in Caenorhabditis elegans.
  Genetics, 161, 133-142.  
12057950 J.Téllez-Sosa, N.Soberón, A.Vega-Segura, M.E.Torres-Márquez, and M.A.Cevallos (2002).
The Rhizobium etli cyaC product: characterization of a novel adenylate cyclase class.
  J Bacteriol, 184, 3560-3568.  
11876648 S.Kazerounian, G.M.Pitari, I.Ruiz-Stewart, S.Schulz, and S.A.Waldman (2002).
Nitric oxide activation of soluble guanylyl cyclase reveals high and low affinity sites that mediate allosteric inhibition by calcium.
  Biochemistry, 41, 3396-3404.  
11157750 B.Bieger, and L.O.Essen (2001).
Structural analysis of adenylate cyclases from Trypanosoma brucei in their monomeric state.
  EMBO J, 20, 433-445.
PDB codes: 1fx2 1fx4
11181955 B.Wedel, and D.Garbers (2001).
The guanylyl cyclase family at Y2K.
  Annu Rev Physiol, 63, 215-233.  
11264454 J.Hanoune, and N.Defer (2001).
Regulation and role of adenylyl cyclase isoforms.
  Annu Rev Pharmacol Toxicol, 41, 145-174.  
11119645 J.Pei, and N.V.Grishin (2001).
GGDEF domain is homologous to adenylyl cyclase.
  Proteins, 42, 210-216.  
11500361 J.Roelofs, M.Meima, P.Schaap, and P.J.Van Haastert (2001).
The Dictyostelium homologue of mammalian soluble adenylyl cyclase encodes a guanylyl cyclase.
  EMBO J, 20, 4341-4348.  
11447108 Y.L.Guo, T.Seebacher, U.Kurz, J.U.Linder, and J.E.Schultz (2001).
Adenylyl cyclase Rv1625c of Mycobacterium tuberculosis: a progenitor of mammalian adenylyl cyclases.
  EMBO J, 20, 3667-3675.  
10713527 B.Bieger, and L.O.Essen (2000).
Crystallization and preliminary X-ray analysis of the catalytic domain of the adenylate cyclase GRESAG4.1 from Trypanosoma brucei.
  Acta Crystallogr D Biol Crystallogr, 56, 359-362.  
10851002 J.A.Ochoa De Alda, G.Ajlani, and J.Houmard (2000).
Synechocystis strain PCC 6803 cya2, a prokaryotic gene that encodes a guanylyl cyclase.
  J Bacteriol, 182, 3839-3842.  
11123935 K.Vijayachandra, M.Guruprasad, R.Bhandari, U.H.Manjunath, B.P.Somesh, N.Srinivasan, K.Suguna, and S.S.Visweswariah (2000).
Biochemical characterization of the intracellular domain of the human guanylyl cyclase C receptor provides evidence for a catalytically active homotrimer.
  Biochemistry, 39, 16075-16083.  
11027131 T.Duda, V.Venkataraman, A.Jankowska, C.Lange, K.W.Koch, and R.K.Sharma (2000).
Impairment of the rod outer segment membrane guanylate cyclase dimerization in a cone-rod dystrophy results in defective calcium signaling.
  Biochemistry, 39, 12522-12533.  
10563809 A.Friebe, M.Russwurm, E.Mergia, and D.Koesling (1999).
A point-mutated guanylyl cyclase with features of the YC-1-stimulated enzyme: implications for the YC-1 binding site?
  Biochemistry, 38, 15253-15257.  
10430891 C.L.Tucker, S.C.Woodcock, R.E.Kelsell, V.Ramamurthy, D.M.Hunt, and J.B.Hurley (1999).
Biochemical analysis of a dimerization domain mutation in RetGC-1 associated with dominant cone-rod dystrophy.
  Proc Natl Acad Sci U S A, 96, 9039-9044.  
10079086 S.Weitmann, N.Würsig, J.M.Navarro, and C.Kleuss (1999).
A functional chimera of mammalian guanylyl and adenylyl cyclases.
  Biochemistry, 38, 3409-3413.  
10101967 W.F.Simonds (1999).
G protein regulation of adenylate cyclase.
  Trends Pharmacol Sci, 20, 66-73.  
9600905 C.L.Tucker, J.H.Hurley, T.R.Miller, and J.B.Hurley (1998).
Two amino acid substitutions convert a guanylyl cyclase, RetGC-1, into an adenylyl cyclase.
  Proc Natl Acad Sci U S A, 95, 5993-5997.  
9724641 H.C.Korswagen, A.M.van der Linden, and R.H.Plasterk (1998).
G protein hyperactivation of the Caenorhabditis elegans adenylyl cyclase SGS-1 induces neuronal degeneration.
  EMBO J, 17, 5059-5065.  
9914257 J.H.Hurley (1998).
The adenylyl and guanylyl cyclase superfamily.
  Curr Opin Struct Biol, 8, 770-777.  
9914249 J.J.Tesmer, and S.R.Sprang (1998).
The structure, catalytic mechanism and regulation of adenylyl cyclase.
  Curr Opin Struct Biol, 8, 713-719.  
9836582 P.E.Brandish, W.Buechler, and M.A.Marletta (1998).
Regeneration of the ferrous heme of soluble guanylate cyclase from the nitric oxide complex: acceleration by thiols and oxyhemoglobin.
  Biochemistry, 37, 16898-16907.  
9698373 R.P.Laura, and J.B.Hurley (1998).
The kinase homology domain of retinal guanylyl cyclases 1 and 2 specifies the affinity and cooperativity of interaction with guanylyl cyclase activating protein-2.
  Biochemistry, 37, 11264-11271.  
9819210 T.Mitterauer, M.Hohenegger, W.J.Tang, C.Nanoff, and M.Freissmuth (1998).
The C2 catalytic domain of adenylyl cyclase contains the second metal ion (Mn2+) binding site.
  Biochemistry, 37, 16183-16191.  
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.

 

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