Crystallization and preliminary X-ray analysis of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase from Staphylococcus aureus.
6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the Mg(2+)-dependent transfer of pyrophosphate from ATP to 6-hydroxymethyl-7,8-dihydropterin (HMDP), forming 6-hydroxymethyl-7,8-dihydropterin pyrophosphate, which is a critical step in the de novo folic acid-biosynthesis pathway. Diffraction-quality crystals of HPPK from the medically relevant species Staphylococcus aureus were grown in the presence of ammonium sulfate or sodium malonate and diffracted to better than 1.65 A resolution. The crystals belonged to space group P2(1), with unit-cell parameters a = 36.8, b = 76.6, c = 51.5 A, alpha = gamma = 90.0, beta = 100.2 degrees . The crystals contained two molecules per asymmetric unit, with a volume per protein weight (V(M)) of 2.04 A(3) Da(-1) and an estimated solvent content of 39.6%.
Chhabra
Sandeep
S
Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.
Newman
Janet
J
Peat
Thomas S
TS
Fernley
Ross T
RT
Caine
Joanne
J
Simpson
Jamie S
JS
Swarbrick
James D
JD
D003460:Crystallization; D018360:Crystallography, X-Ray; D017854:Diphosphotransferases / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000201:enzymology*
D017854:Diphosphotransferases; C019684:2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase
Science. 1992 Aug 21;257(5073):1064-73
1509257
Structure. 2004 Sep;12(9):1705-17
15341734
Science. 1994 Apr 15;264(5157):382-8
8153625
Arch Biochem Biophys. 1989 Mar;269(2):371-80
2645826
Science. 1994 Apr 15;264(5157):375-82
8153624
Trends Microbiol. 1994 Oct;2(10):422-5
7850213
J Mol Biol. 2009 Apr 17;387(5):1298-308
19249312
Biochemistry. 2009 Jan 20;48(2):302-12
19108643
J Mol Biol. 1999 Mar 26;287(2):211-9
10080886
Pharmacotherapy. 2007 Feb;27(2):227-49
17253914
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008 Nov 1;64(Pt 11):991-6
18997323
Ann Pharmacother. 2004 Feb;38(2):338-41
14742775
Bioessays. 2002 Jul;24(7):637-48
12111724
N Engl J Med. 2005 Apr 7;352(14):1485-7
15814886
Antimicrob Agents Chemother. 2007 Feb;51(2):423-8
17116664
Structure. 2004 Mar;12(3):467-75
15016362
Science. 1992 Aug 21;257(5073):1050-5
1509255
Vitam Horm. 2008;79:411-33
18804704
Acta Crystallogr D Biol Crystallogr. 1999 May;55(Pt 5):988-93
10216295
J Mol Biol. 1968 Apr 28;33(2):491-7
5700707