PDBsum entry 1nh8

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Transferase PDB id
Protein chain
276 a.a. *
SO4 ×3
Waters ×236
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Atp phosphoribosyltransferase (atp-prtase) from mycobacteriu tuberculosis in complex with amp and histidine
Structure: Atp phosphoribosyltransferase. Chain: a. Engineered: yes
Source: Mycobacterium tuberculosis h37rv. Organism_taxid: 83332. Strain: h37rv. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Hexamer (from PDB file)
1.80Å     R-factor:   0.199     R-free:   0.236
Authors: Y.Cho,V.Sharma,J.C.Sacchettini,Tb Structural Genomics Consor (Tbsgc)
Key ref:
Y.Cho et al. (2003). Crystal structure of ATP phosphoribosyltransferase from Mycobacterium tuberculosis. J Biol Chem, 278, 8333-8339. PubMed id: 12511575 DOI: 10.1074/jbc.M212124200
18-Dec-02     Release date:   11-Feb-03    
Go to PROCHECK summary

Protein chain
P9WMN1  (HIS1_MYCTU) -  ATP phosphoribosyltransferase
284 a.a.
276 a.a.
Key:    Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Atp phosphoribosyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Histidine Biosynthesis (early stages)
      Reaction: 1-(5-phospho-beta-D-ribosyl)-ATP + diphosphate = ATP + 5-phospho-alpha-D- ribose 1-diphosphate
+ diphosphate
Bound ligand (Het Group name = AMP)
matches with 74.19% similarity
+ 5-phospho-alpha-D- ribose 1-diphosphate
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     cellular amino acid biosynthetic process   2 terms 
  Biochemical function     nucleotide binding     7 terms  


DOI no: 10.1074/jbc.M212124200 J Biol Chem 278:8333-8339 (2003)
PubMed id: 12511575  
Crystal structure of ATP phosphoribosyltransferase from Mycobacterium tuberculosis.
Y.Cho, V.Sharma, J.C.Sacchettini.
The N-1-(5'-phosphoribosyl)-ATP transferase catalyzes the first step of the histidine biosynthetic pathway and is regulated by a feedback mechanism by the product histidine. The crystal structures of the N-1-(5'-phosphoribosyl)-ATP transferase from Mycobacterium tuberculosis in complex with inhibitor histidine and AMP has been determined to 1.8 A resolution and without ligands to 2.7 A resolution. The active enzyme exists primarily as a dimer, and the histidine-inhibited form is a hexamer. The structure represents a new fold for a phosphoribosyltransferase, consisting of three continuous domains. The inhibitor AMP binds in the active site cavity formed between the two catalytic domains. A model for the mechanism of allosteric inhibition has been derived from conformational differences between the AMP:His-bound and apo structures.
  Selected figure(s)  
Figure 1.
Fig. 1. The overall fold of the mtATP-PRTase. a, stereo view of the ribbon representation of the mtATP-PRTase protomer. Ribbon is colored by secondary structure with yellow for helices, cyan for sheets, and gray for coils. The ligand AMP and His are shown in ball-and-stick representation colored by type of atom. The ribbon diagram was prepared by MOLSCRIPT (47) and Raster3d (48). b, molecular surface of an ATP-PRTase protomer colored by electrostatic potential. AMP was located in the cleft between domains I and II and the histidine on the allosteric regulatory domain. c and d, electron density of bound AMP (c) and histidine (d). Shake&Warp (26) electron density map was averaged from six independent refinements of a composite model. This and all the remaining figures were prepared by SPOCK (
Figure 5.
Fig. 5. Binding of histidine in the allosteric site and its affect on lysis of disulfide. a, ribbon representation of the histidine-binding region. Residues involved in binding histidine in domain III from two adjacent subunits are shown in blue and red ribbons. The residues involved in direct interactions with histidine are shown in a stick representation. b, superimposition of the apo form (cyan ribbon) and AMP:His form (red ribbon) showing the conformational differences observed near the disulfide bond. The bound AMP in the active site is shown as a ball-and-stick representation.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 8333-8339) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19486323 J.D.Rees, R.A.Ingle, and J.A.Smith (2009).
Relative contributions of nine genes in the pathway of histidine biosynthesis to the control of free histidine concentrations in Arabidopsis thaliana.
  Plant Biotechnol J, 7, 499-511.  
18368466 J.Siltberg-Liberles, and A.Martinez (2009).
Searching distant homologs of the regulatory ACT domain in phenylalanine hydroxylase.
  Amino Acids, 36, 235-249.  
19351325 P.Zhang, J.Ma, Z.Zhang, M.Zha, H.Xu, G.Zhao, and J.Ding (2009).
Molecular basis of the inhibitor selectivity and insights into the feedback inhibition mechanism of citramalate synthase from Leptospira interrogans.
  Biochem J, 421, 133-143.
PDB codes: 3f6g 3f6h
18778048 Y.Cho, T.R.Ioerger, and J.C.Sacchettini (2008).
Discovery of novel nitrobenzothiazole inhibitors for Mycobacterium tuberculosis ATP phosphoribosyl transferase (HisG) through virtual screening.
  J Med Chem, 51, 5984-5992.  
17586767 M.H.Godsey, G.Minasov, L.Shuvalova, J.S.Brunzelle, I.I.Vorontsov, F.R.Collart, and W.F.Anderson (2007).
The 2.2 A resolution crystal structure of Bacillus cereus Nif3-family protein YqfO reveals a conserved dimetal-binding motif and a regulatory domain.
  Protein Sci, 16, 1285-1293.
PDB code: 2gx8
17362499 S.Gonin, P.Arnoux, B.Pierru, J.Lavergne, B.Alonso, M.Sabaty, and D.Pignol (2007).
Crystal structures of an Extracytoplasmic Solute Receptor from a TRAP transporter in its open and closed forms reveal a helix-swapped dimer requiring a cation for alpha-keto acid binding.
  BMC Struct Biol, 7, 11.
PDB codes: 2hzk 2hzl
17154531 K.S.Champagne, E.Piscitelli, and C.S.Francklyn (2006).
Substrate recognition by the hetero-octameric ATP phosphoribosyltransferase from Lactococcus lactis.
  Biochemistry, 45, 14933-14943.  
17187687 K.S.Saikatendu, X.Zhang, L.Kinch, M.Leybourne, N.V.Grishin, and H.Zhang (2006).
Structure of a conserved hypothetical protein SA1388 from S. aureus reveals a capped hexameric toroid with two PII domain lids and a dinuclear metal center.
  BMC Struct Biol, 6, 27.
PDB codes: 2nyd 3lnl
16478688 V.L.Arcus, J.S.Lott, J.M.Johnston, and E.N.Baker (2006).
The potential impact of structural genomics on tuberculosis drug discovery.
  Drug Discov Today, 11, 28-34.  
16363798 G.A.Grant, Z.Hu, and X.L.Xu (2005).
Identification of amino acid residues contributing to the mechanism of cooperativity in Escherichia coli D-3-phosphoglycerate dehydrogenase.
  Biochemistry, 44, 16844-16852.  
16154095 J.S.Chappie, J.M.Cànaves, G.W.Han, C.L.Rife, Q.Xu, and R.C.Stevens (2005).
The structure of a eukaryotic nicotinic acid phosphoribosyltransferase reveals structural heterogeneity among type II PRTases.
  Structure, 13, 1385-1396.
PDB code: 1vlp
15660995 M.C.Vega, P.Zou, F.J.Fernandez, G.E.Murphy, R.Sterner, A.Popov, and M.Wilmanns (2005).
Regulation of the hetero-octameric ATP phosphoribosyl transferase complex from Thermotoga maritima by a tRNA synthetase-like subunit.
  Mol Microbiol, 55, 675-686.
PDB code: 1usy
15159544 N.Koon, C.J.Squire, and E.N.Baker (2004).
Crystal structure of LeuA from Mycobacterium tuberculosis, a key enzyme in leucine biosynthesis.
  Proc Natl Acad Sci U S A, 101, 8295-8300.
PDB codes: 1sr9 3fig
14675542 C.V.Smith, and J.C.Sacchettini (2003).
Mycobacterium tuberculosis: a model system for structural genomics.
  Curr Opin Struct Biol, 13, 658-664.  
12970756 E.R.Schreiter, M.D.Sintchak, Y.Guo, P.T.Chivers, R.T.Sauer, and C.L.Drennan (2003).
Crystal structure of the nickel-responsive transcription factor NikR.
  Nat Struct Biol, 10, 794-799.
PDB codes: 1q5v 1q5y
12915092 M.Bellinzoni, and G.Riccardi (2003).
Techniques and applications: The heterologous expression of Mycobacterium tuberculosis genes is an uphill road.
  Trends Microbiol, 11, 351-358.  
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.