PMID- 32148856
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231113
IS  - 2052-2525 (Print)
IS  - 2052-2525 (Electronic)
IS  - 2052-2525 (Linking)
VI  - 7
IP  - Pt 2
DP  - 2020 Mar 1
TI  - Structure and mechanism of copper-carbonic anhydrase II: a nitrite reductase.
PG  - 287-293
LID - 10.1107/S2052252520000986 [doi]
AB  - Nitric oxide (NO) promotes vasodilation through the activation of guanylate 
      cyclase, resulting in the relaxation of the smooth muscle vasculature and a 
      subsequent decrease in blood pressure. Therefore, its regulation is of interest 
      for the treatment and prevention of heart disease. An example is pulmonary 
      hypertension which is treated by targeting this NO/vasodilation pathway. In 
      bacteria, plants and fungi, nitrite (NO(2) (-)) is utilized as a source of NO 
      through enzymes known as nitrite reductases. These enzymes reduce NO(2) (-) to NO 
      through a catalytic metal ion, often copper. Recently, several studies have shown 
      nitrite reductase activity of mammalian carbonic anhydrase II (CAII), yet the 
      molecular basis for this activity is unknown. Here we report the crystal 
      structure of copper-bound human CAII (Cu-CAII) in complex with NO(2) (-) at 1.2 A 
      resolution. The structure exhibits Type 1 (T-1) and 2 (T-2) copper centers, 
      analogous to bacterial nitrite reductases, both required for catalysis. The 
      copper-substituted CAII active site is penta-coordinated with a 'side-on' bound 
      NO(2) (-), resembling a T-2 center. At the N terminus, several residues that are 
      normally disordered form a porphyrin ring-like configuration surrounding a second 
      copper, acting as a T-1 center. A structural comparison with both apo- (without 
      metal) and zinc-bound CAII (Zn-CAII) provides a mechanistic picture of how, in 
      the presence of copper, CAII, with minimal conformational changes, can function 
      as a nitrite reductase.
CI  - (c) Andring et al. 2020.
FAU - Andring, Jacob T
AU  - Andring JT
AD  - Department of Biochemistry and Molecular Biology, College of Medicine, University 
      of Florida, Gainesville, FL 32610 USA.
FAU - Kim, Chae Un
AU  - Kim CU
AD  - Department of Physics, Ulsan National Institute of Science and Technology 
      (UNIST), Ulsan 44919, Republic of Korea.
FAU - McKenna, Robert
AU  - McKenna R
AD  - Department of Biochemistry and Molecular Biology, College of Medicine, University 
      of Florida, Gainesville, FL 32610 USA.
LA  - eng
PT  - Journal Article
DEP - 20200221
PL  - England
TA  - IUCrJ
JT  - IUCrJ
JID - 101623101
EIN - IUCrJ. 2021 Jan 18;8(Pt 2):329. PMID: 33708409
PMC - PMC7055381
OTO - NOTNLM
OT  - X-ray crystallography
OT  - apo-carbonic anhydrase II
OT  - catalytic metal ions
OT  - copper-carbonic anhydrase II
OT  - nitric oxide
OT  - nitrite reductases
EDAT- 2020/03/10 06:00
MHDA- 2020/03/10 06:01
PMCR- 2020/02/21
CRDT- 2020/03/10 06:00
PHST- 2019/10/30 00:00 [received]
PHST- 2020/01/24 00:00 [accepted]
PHST- 2020/03/10 06:00 [entrez]
PHST- 2020/03/10 06:00 [pubmed]
PHST- 2020/03/10 06:01 [medline]
PHST- 2020/02/21 00:00 [pmc-release]
AID - lz5032 [pii]
AID - 10.1107/S2052252520000986 [doi]
PST - epublish
SO  - IUCrJ. 2020 Feb 21;7(Pt 2):287-293. doi: 10.1107/S2052252520000986. eCollection 
      2020 Mar 1.