2W5M

RNASE A-PYROPHOSPHATE ION COMPLEX

Summary for 2W5M

• Entry DOI: 10.2210/pdb2w5m/pdb
• Related: 1A2W 1A5P 1A5Q 1AFK 1AFL 1AFU 1AQP 1B6V 1BEL 1BZQ 1C0B 1C0C 1C8W 1C9V 1C9X 1CJQ 1CJR 1D5D 1D5E 1D5H 1DFJ 1DY5 1EIC 1EID 1EIE 1EOS 1EOW 1F0V 1FEV 1FS3 1GV7 1IZP 1IZQ 1IZR 1J7Z 1J80 1J81 1J82 1JN4 1JS0 1JVT 1JVU 1JVV 1KF2 1KF3 1KF4 1KF5 1KF7 1KF8 1KH8 1LSQ 1O0F 1O0H 1O0M 1O0N 1O0O 1QHC 1RAR 1RAS 1RAT 1RBB 1RBC 1RBD 1RBE 1RBF 1RBG 1RBH 1RBI 1RBJ 1RBN 1RBW 1RBX 1RCA 1RCN 1RHA 1RHB 1RNC 1RND 1RNM 1RNN 1RNO 1RNQ 1RNU 1RNV 1RNW 1RNX 1RNY 1RNZ 1ROB 1RPF 1RPG 1RPH 1RSM 1RTA 1RTB 1RUV 1SRN 1SSA 1SSB 1SSC 1U1B 1W4O 1W4P 1W4Q 1WBU 1XPS 1XPT 1YMN 1YMR 1YMW 1Z3L 1Z3M 1Z3P 1Z6D 1Z6S 2AAS 2APQ 2BLP 2BLZ 2RAT 2RLN 2RNS 2W5G 2W5I 2W5K 2W5L 3RAT 3RN3 3RSD 3RSK 3RSP 3SRN 4RAT 4RSD 4RSK 4SRN 5RAT 5RSA 6RAT 7RAT 8RAT 8RSA 9RAT 9RSA
• Descriptor: RIBONUCLEASE PANCREATIC, PYROPHOSPHATE 2- (3 entities in total)
• Functional Keywords: hydrolase, inhibitor, glycoprotein, anion, nuclease, secreted, glycation, endonuclease
• Biological source: BOS TAURUS (CATTLE)
• Cellular location: Secreted: P61823
• Total number of polymer chains: 2
• Total formula weight: 27768.57

Authors

Chavali, G.B.,Holloway, D.E.,Baker, M.D.,Acharya, K.R. (deposition date: 2008-12-10, release date: 2009-02-17, Last modification date: 2023-12-13)

Primary citation

Holloway, D.E.,Chavali, G.B.,Leonidas, D.D.,Baker, M.D.,Acharya, K.R.
Influence of Naturally-Occurring 5'-Pyrophosphate-Linked Substituents on the Binding of Adenylic Inhibitors to Ribonuclease A: An X-Ray Crystallographic Study.
Biopolymers, 91:995-, 2009

PubMed Abstract: Ribonuclease A is the archetype of a functionally diverse superfamily of vertebrate-specific ribonucleases. Inhibitors of its action have potential use in the elucidation of the in vivo roles of these enzymes and in the treatment of pathologies associated therewith. Derivatives of adenosine 5'-pyrophosphate are the most potent nucleotide-based inhibitors known. Here, we use X-ray crystallography to visualize the binding of four naturally-occurring derivatives that contain 5'-pyrophosphate-linked extensions. 5'-ATP binds with the adenine occupying the B(2) subsite in the manner of an RNA substrate but with the gamma-phosphate at the P(1) subsite. Diadenosine triphosphate (Ap(3)A) binds with the adenine in syn conformation, the beta-phosphate as the principal P(1) subsite ligand and without order beyond the gamma-phosphate. NADPH and NADP(+) bind with the adenine stacked against an alternative rotamer of His119, the 2'-phosphate at the P(1) subsite, and without order beyond the 5'-alpha-phosphate. We also present the structure of the complex formed with pyrophosphate ion. The structural data enable existing kinetic data on the binding of these compounds to a variety of ribonucleases to be rationalized and suggest that as the complexity of the 5'-linked extension increases, the need to avoid unfavorable contacts places limitations on the number of possible binding modes.

PubMed: 19191310
DOI: 10.1002/BIP.21158

Experimental method

X-RAY DIFFRACTION (1.8 Å)